|
|
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 6;code = 54
char = /;code = 47
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 3;code = 51
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = .;code = 46
result sql = ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB.
ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB.char = <;code = 60
char = b;code = 98
char = >;code = 62
char = P;code = 80
char = U;code = 85
char = R;code = 82
char = P;code = 80
char = O;code = 79
char = S;code = 83
char = E;code = 69
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;;code = 59
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = I;code = 73
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char = h;code = 104
char = i;code = 105
char = s;code = 115
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char = s;code = 115
char = t;code = 116
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char = d;code = 100
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char = ,;code = 44
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char = w;code = 119
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = E;code = 69
char = X;code = 88
char = P;code = 80
char = E;code = 69
char = R;code = 82
char = I;code = 73
char = M;code = 77
char = E;code = 69
char = N;code = 78
char = T;code = 84
char = A;code = 65
char = L;code = 76
char = ;code = 32
char = D;code = 68
char = E;code = 69
char = S;code = 83
char = I;code = 73
char = G;code = 71
char = N;code = 78
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = i;code = 105
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char = e;code = 101
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char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = i;code = 105
char = n;code = 110
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char = 6;code = 54
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 6;code = 54
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char = ,;code = 44
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char = d;code = 100
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = r;code = 114
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char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
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char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = (;code = 40
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 3;code = 51
char = );code = 41
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char = i;code = 105
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char = ;code = 32
char = p;code = 112
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char = e;code = 101
char = a;code = 97
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char = c;code = 99
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char = c;code = 99
char = a;code = 97
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char = c;code = 99
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char = r;code = 114
char = ;code = 32
char = x;code = 120
char = e;code = 101
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char = o;code = 111
char = g;code = 103
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char = a;code = 97
char = f;code = 102
char = t;code = 116
char = s;code = 115
char = ;code = 32
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char = c;code = 99
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char = P;code = 80
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char = ,;code = 44
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char = i;code = 105
char = o;code = 111
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char = P;code = 80
char = l;code = 108
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char = x;code = 120
char = ;code = 32
char = c;code = 99
char = y;code = 121
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char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = s;code = 115
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char = o;code = 111
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char = g;code = 103
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char = e;code = 101
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char = b;code = 98
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char = a;code = 97
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char = o;code = 111
char = m;code = 109
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char = e;code = 101
char = r;code = 114
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char = s;code = 115
char = a;code = 97
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char = a;code = 97
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char = l;code = 108
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char = e;code = 101
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char = C;code = 67
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char = (;code = 40
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char = P;code = 80
char = C;code = 67
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char = r;code = 114
char = o;code = 111
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char = p;code = 112
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char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = h;code = 104
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char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = a;code = 97
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char = a;code = 97
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char = t;code = 116
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char = a;code = 97
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char = o;code = 111
char = r;code = 114
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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char = c;code = 99
char = l;code = 108
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char = D;code = 68
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = i;code = 105
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char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = M;code = 77
char = I;code = 73
char = A;code = 65
char = -;code = 45
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
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char = A;code = 65
char = S;code = 83
char = P;code = 80
char = C;code = 67
char = -;code = 45
char = s;code = 115
char = h;code = 104
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = s;code = 115
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char = L;code = 76
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char = a;code = 97
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char = t;code = 116
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char = a;code = 97
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char = a;code = 97
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char = r;code = 114
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char = A;code = 65
char = T;code = 84
char = 3;code = 51
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char = w;code = 119
char = a;code = 97
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char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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char = o;code = 111
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char = b;code = 98
char = e;code = 101
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char = s;code = 115
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char = g;code = 103
char = n;code = 110
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char = f;code = 102
char = i;code = 105
char = c;code = 99
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char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = Z;code = 90
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = A;code = 65
char = S;code = 83
char = P;code = 80
char = C;code = 67
char = -;code = 45
char = s;code = 115
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char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
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char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = v;code = 118
char = e;code = 101
char = r;code = 114
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char = x;code = 120
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char = s;code = 115
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char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = Z;code = 90
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char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = d;code = 100
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char = a;code = 97
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char = 7;code = 55
char = 5;code = 53
char = %;code = 37
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char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = o;code = 111
char = f;code = 102
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char = I;code = 73
char = L;code = 76
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char = 6;code = 54
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char = p;code = 112
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char = o;code = 111
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char = o;code = 111
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char = ;code = 32
char = C;code = 67
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = O;code = 79
char = u;code = 117
char = r;code = 114
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char = s;code = 115
char = t;code = 116
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char = g;code = 103
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char = h;code = 104
char = a;code = 97
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char = Z;code = 90
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char = P;code = 80
char = 4;code = 52
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char = o;code = 111
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char = a;code = 97
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char = S;code = 83
char = T;code = 84
char = A;code = 65
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char = P;code = 80
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char = a;code = 97
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result sql = PURPOSE : Recent studies indicate a strong correlation of zinc transporter ZIP4 and pancreatic cancer progression; however, the underlying mechanisms are unclear. We have recently found that ZIP4 is overexpressed in pancreatic cancer. In this study, we investigated the signaling pathway through which ZIP4 regulates pancreatic cancer growth.
EXPERIMENTAL DESIGN : The expression of cyclin D1, interleukin 6 (IL-6), and signal transducer and activator of transcription 3 (STAT3) in pancreatic cancer xenografts and cells were examined by real-time PCR, Bio-Plex cytokine assay, and Western blot, respectively. The activity of cAMP response element-binding protein (CREB) is examined by a promoter activity assay.
RESULTS : Cyclin D1 was significantly increased in the ZIP4 overexpressing MIA PaCa-2 cells (MIA-ZIP4)-injected orthotopic xenografts and was downregulated in the ZIP4-silenced ASPC-1 (ASPC-shZIP4) group. The phosphorylation of STAT3, an upstream activator of cyclin D1, was increased in MIA-ZIP4 cells and decreased in ASPC-shZIP4 cells. IL-6, a known upstream activator for STAT3, was also found to be significantly increased in the MIA-ZIP4 cells and xenografts and decreased in the ASPC-shZIP4 group. Overexpression of ZIP4 led to a 75% increase of IL-6 promoter activity and caused increased phosphorylation of CREB.
CONCLUSIONS : Our study suggest that ZIP4 overexpression causes increased IL-6 transcription through CREB, which in turn activates STAT3 and leads to increased cyclin D1 expression, resulting in increased cell proliferation and tumor progression in pancreatic cancer. These results elucidated a novel pathway in ZIP4-mediated pancreatic cancer growth and suggest new therapeutic targets, including ZIP4, IL-6, and STAT3, in pancreatic cancer treatment.
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result sql = ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB.
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char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
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char = ;code = 32
char = c;code = 99
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char = r;code = 114
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char = s;code = 115
char = p;code = 112
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char = s;code = 115
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char = e;code = 101
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char = e;code = 101
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char = d;code = 100
char = i;code = 105
char = n;code = 110
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char = t;code = 116
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char = R;code = 82
char = E;code = 69
char = B;code = 66
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char = s;code = 115
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char = c;code = 99
char = t;code = 116
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char = v;code = 118
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char = s;code = 115
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char = <;code = 60
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char = S;code = 83
char = U;code = 85
char = L;code = 76
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char = S;code = 83
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char = ;code = 32
char = s;code = 115
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char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = t;code = 116
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char = i;code = 105
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char = a;code = 97
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char = h;code = 104
char = e;code = 101
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char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = o;code = 111
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char = e;code = 101
char = x;code = 120
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char = s;code = 115
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char = I;code = 73
char = A;code = 65
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char = P;code = 80
char = a;code = 97
char = C;code = 67
char = a;code = 97
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char = 2;code = 50
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = (;code = 40
char = M;code = 77
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char = j;code = 106
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char = c;code = 99
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char = e;code = 101
char = d;code = 100
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char = o;code = 111
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = f;code = 102
char = t;code = 116
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = -;code = 45
char = s;code = 115
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = A;code = 65
char = S;code = 83
char = P;code = 80
char = C;code = 67
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char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = A;code = 65
char = S;code = 83
char = P;code = 80
char = C;code = 67
char = -;code = 45
char = s;code = 115
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char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = );code = 41
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = S;code = 83
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char = A;code = 65
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char = 3;code = 51
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = u;code = 117
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char = t;code = 116
char = r;code = 114
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = o;code = 111
char = r;code = 114
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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char = c;code = 99
char = l;code = 108
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char = n;code = 110
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char = D;code = 68
char = 1;code = 49
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char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = i;code = 105
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char = c;code = 99
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
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char = M;code = 77
char = I;code = 73
char = A;code = 65
char = -;code = 45
char = Z;code = 90
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char = P;code = 80
char = 4;code = 52
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
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char = a;code = 97
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char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = A;code = 65
char = S;code = 83
char = P;code = 80
char = C;code = 67
char = -;code = 45
char = s;code = 115
char = h;code = 104
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = I;code = 73
char = L;code = 76
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char = ;code = 32
char = a;code = 97
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char = k;code = 107
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char = o;code = 111
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char = u;code = 117
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = m;code = 109
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char = a;code = 97
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char = v;code = 118
char = a;code = 97
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char = o;code = 111
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 3;code = 51
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char = s;code = 115
char = o;code = 111
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char = f;code = 102
char = o;code = 111
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char = n;code = 110
char = d;code = 100
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char = t;code = 116
char = o;code = 111
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char = b;code = 98
char = e;code = 101
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char = s;code = 115
char = i;code = 105
char = g;code = 103
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char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = i;code = 105
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char = c;code = 99
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char = a;code = 97
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char = e;code = 101
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char = i;code = 105
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = M;code = 77
char = I;code = 73
char = A;code = 65
char = -;code = 45
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = o;code = 111
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char = r;code = 114
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
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char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = A;code = 65
char = S;code = 83
char = P;code = 80
char = C;code = 67
char = -;code = 45
char = s;code = 115
char = h;code = 104
char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = Z;code = 90
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char = P;code = 80
char = 4;code = 52
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = d;code = 100
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char = a;code = 97
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char = 7;code = 55
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char = e;code = 101
char = a;code = 97
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char = o;code = 111
char = f;code = 102
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char = I;code = 73
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char = C;code = 67
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char = E;code = 69
char = B;code = 66
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
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char = >;code = 62
char = <;code = 60
char = b;code = 98
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char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = O;code = 79
char = u;code = 117
char = r;code = 114
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char = s;code = 115
char = t;code = 116
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char = g;code = 103
char = g;code = 103
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = Z;code = 90
char = I;code = 73
char = P;code = 80
char = 4;code = 52
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char = o;code = 111
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char = e;code = 101
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char = s;code = 115
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char = o;code = 111
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char = s;code = 115
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char = s;code = 115
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 6;code = 54
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = c;code = 99
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char = p;code = 112
char = t;code = 116
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char = C;code = 67
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = ,;code = 44
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char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
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char = t;code = 116
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char = r;code = 114
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = e;code = 101
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char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = 3;code = 51
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char = o;code = 111
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char = i;code = 105
char = n;code = 110
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result sql = PURPOSE : Recent studies indicate a strong correlation of zinc transporter ZIP4 and pancreatic cancer progression; however, the underlying mechanisms are unclear. We have recently found that ZIP4 is overexpressed in pancreatic cancer. In this study, we investigated the signaling pathway through which ZIP4 regulates pancreatic cancer growth.
EXPERIMENTAL DESIGN : The expression of cyclin D1, interleukin 6 (IL-6), and signal transducer and activator of transcription 3 (STAT3) in pancreatic cancer xenografts and cells were examined by real-time PCR, Bio-Plex cytokine assay, and Western blot, respectively. The activity of cAMP response element-binding protein (CREB) is examined by a promoter activity assay.
RESULTS : Cyclin D1 was significantly increased in the ZIP4 overexpressing MIA PaCa-2 cells (MIA-ZIP4)-injected orthotopic xenografts and was downregulated in the ZIP4-silenced ASPC-1 (ASPC-shZIP4) group. The phosphorylation of STAT3, an upstream activator of cyclin D1, was increased in MIA-ZIP4 cells and decreased in ASPC-shZIP4 cells. IL-6, a known upstream activator for STAT3, was also found to be significantly increased in the MIA-ZIP4 cells and xenografts and decreased in the ASPC-shZIP4 group. Overexpression of ZIP4 led to a 75% increase of IL-6 promoter activity and caused increased phosphorylation of CREB.
CONCLUSIONS : Our study suggest that ZIP4 overexpression causes increased IL-6 transcription through CREB, which in turn activates STAT3 and leads to increased cyclin D1 expression, resulting in increased cell proliferation and tumor progression in pancreatic cancer. These results elucidated a novel pathway in ZIP4-mediated pancreatic cancer growth and suggest new therapeutic targets, including ZIP4, IL-6, and STAT3, in pancreatic cancer treatment.
Publication: Clin. Cancer Res. 2010 Mar 1 ;16(5)::1423-30.
Publication Date: 2010 Mar 1
Study Author(s): Zhang, Yuqing;Bharadwaj, Uddalak;Logsdon, Craig D;Chen, Changyi;Yao, Qizhi;Li, Min;
Institution: Michael E DeBakey Department of Surgery, Baylor College of Medicine, Molecular Surgeon Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shortcut link to this study:
Publication Date: 2010 Mar 1
Study Author(s): Zhang, Yuqing;Bharadwaj, Uddalak;Logsdon, Craig D;Chen, Changyi;Yao, Qizhi;Li, Min;
Institution: Michael E DeBakey Department of Surgery, Baylor College of Medicine, Molecular Surgeon Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shortcut link to this study:
PURPOSE : Recent studies indicate a strong correlation of zinc transporter ZIP4 and pancreatic cancer progression; however, the underlying mechanisms are unclear. We have recently found that ZIP4 is overexpressed in pancreatic cancer. In this study, we investigated the signaling pathway through which ZIP4 regulates pancreatic cancer growth.
EXPERIMENTAL DESIGN : The expression of cyclin D1, interleukin 6 (IL-6), and signal transducer and activator of transcription 3 (STAT3) in pancreatic cancer xenografts and cells were examined by real-time PCR, Bio-Plex cytokine assay, and Western blot, respectively. The activity of cAMP response element-binding protein (CREB) is examined by a promoter activity assay.
RESULTS : Cyclin D1 was significantly increased in the ZIP4 overexpressing MIA PaCa-2 cells (MIA-ZIP4)-injected orthotopic xenografts and was downregulated in the ZIP4-silenced ASPC-1 (ASPC-shZIP4) group. The phosphorylation of STAT3, an upstream activator of cyclin D1, was increased in MIA-ZIP4 cells and decreased in ASPC-shZIP4 cells. IL-6, a known upstream activator for STAT3, was also found to be significantly increased in the MIA-ZIP4 cells and xenografts and decreased in the ASPC-shZIP4 group. Overexpression of ZIP4 led to a 75% increase of IL-6 promoter activity and caused increased phosphorylation of CREB.
CONCLUSIONS : Our study suggest that ZIP4 overexpression causes increased IL-6 transcription through CREB, which in turn activates STAT3 and leads to increased cyclin D1 expression, resulting in increased cell proliferation and tumor progression in pancreatic cancer. These results elucidated a novel pathway in ZIP4-mediated pancreatic cancer growth and suggest new therapeutic targets, including ZIP4, IL-6, and STAT3, in pancreatic cancer treatment.
EXPERIMENTAL DESIGN : The expression of cyclin D1, interleukin 6 (IL-6), and signal transducer and activator of transcription 3 (STAT3) in pancreatic cancer xenografts and cells were examined by real-time PCR, Bio-Plex cytokine assay, and Western blot, respectively. The activity of cAMP response element-binding protein (CREB) is examined by a promoter activity assay.
RESULTS : Cyclin D1 was significantly increased in the ZIP4 overexpressing MIA PaCa-2 cells (MIA-ZIP4)-injected orthotopic xenografts and was downregulated in the ZIP4-silenced ASPC-1 (ASPC-shZIP4) group. The phosphorylation of STAT3, an upstream activator of cyclin D1, was increased in MIA-ZIP4 cells and decreased in ASPC-shZIP4 cells. IL-6, a known upstream activator for STAT3, was also found to be significantly increased in the MIA-ZIP4 cells and xenografts and decreased in the ASPC-shZIP4 group. Overexpression of ZIP4 led to a 75% increase of IL-6 promoter activity and caused increased phosphorylation of CREB.
CONCLUSIONS : Our study suggest that ZIP4 overexpression causes increased IL-6 transcription through CREB, which in turn activates STAT3 and leads to increased cyclin D1 expression, resulting in increased cell proliferation and tumor progression in pancreatic cancer. These results elucidated a novel pathway in ZIP4-mediated pancreatic cancer growth and suggest new therapeutic targets, including ZIP4, IL-6, and STAT3, in pancreatic cancer treatment.
PMID: 20160059
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