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result sql = Vitamin D regulates the phenotype of human breast cancer cells.
Vitamin D regulates the phenotype of human breast cancer cells.
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = s;code = 115
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char = a;code = 97
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char = l;code = 108
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
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char = c;code = 99
char = y;code = 121
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char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = e;code = 101
char = x;code = 120
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
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 = a;code = 97
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
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char = g;code = 103
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = a;code = 97
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char = d;code = 100
char = i;code = 105
char = n;code = 110
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char = 7;code = 55
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = o;code = 111
char = n;code = 110
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
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char = O;code = 79
char = H;code = 72
char = );code = 41
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = D;code = 68
char = (;code = 40
char = 3;code = 51
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = d;code = 100
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
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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 = 46
char = ;code = 32
char = A;code = 65
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = D;code = 68
char = (;code = 40
char = 3;code = 51
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
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 = a;code = 97
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
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 = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = (;code = 40
char = v;code = 118
char = );code = 41
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = (;code = 40
char = 5;code = 53
char = );code = 41
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = (;code = 40
char = F;code = 70
char = A;code = 65
char = K;code = 75
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = x;code = 120
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char = l;code = 108
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
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char = m;code = 109
char = i;code = 105
char = t;code = 116
char = a;code = 97
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char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
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
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
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 = t;code = 116
char = h;code = 104
char = e;code = 101
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char = F;code = 70
char = A;code = 65
char = K;code = 75
char = .;code = 46
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = D;code = 68
char = (;code = 40
char = 3;code = 51
char = );code = 41
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = D;code = 68
char = A;code = 65
char = -;code = 45
char = M;code = 77
char = B;code = 66
char = -;code = 45
char = 4;code = 52
char = 5;code = 53
char = 3;code = 51
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = M;code = 77
char = D;code = 68
char = A;code = 65
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char = M;code = 77
char = B;code = 66
char = -;code = 45
char = 4;code = 52
char = 6;code = 54
char = 8;code = 56
char = ;code = 32
char = c;code = 99
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char = l;code = 108
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char = a;code = 97
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char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
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char = i;code = 105
char = c;code = 99
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char = b;code = 98
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char = t;code = 116
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = h;code = 104
char = e;code = 101
char = s;code = 115
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char = o;code = 111
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char = o;code = 111
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char = l;code = 108
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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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 = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = h;code = 104
char = y;code = 121
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char = a;code = 97
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char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = d;code = 100
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = n;code = 110
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = m;code = 109
char = y;code = 121
char = o;code = 111
char = e;code = 101
char = p;code = 112
char = i;code = 105
char = t;code = 116
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char = e;code = 101
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char = a;code = 97
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char = m;code = 109
char = a;code = 97
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char = a;code = 97
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char = b;code = 98
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char = O;code = 79
char = H;code = 72
char = );code = 41
char = (;code = 40
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char = D;code = 68
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char = 3;code = 51
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char = a;code = 97
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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 = e;code = 101
char = r;code = 114
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = l;code = 108
char = i;code = 105
char = n;code = 110
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char = s;code = 115
char = .;code = 46
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char = O;code = 79
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = m;code = 109
char = y;code = 121
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char = e;code = 101
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char = i;code = 105
char = t;code = 116
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char = e;code = 101
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char = i;code = 105
char = a;code = 97
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char = p;code = 112
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char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
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char = s;code = 115
char = u;code = 117
char = c;code = 99
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char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = 6;code = 54
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char = i;code = 105
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char = g;code = 103
char = r;code = 114
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char = n;code = 110
char = ,;code = 44
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char = b;code = 98
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char = a;code = 97
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char = t;code = 116
char = e;code = 101
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char = ,;code = 44
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char = a;code = 97
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char = d;code = 100
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char = o;code = 111
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char = t;code = 116
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char = s;code = 115
char = c;code = 99
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char = a;code = 97
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char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = S;code = 83
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char = A;code = 65
char = );code = 41
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = D;code = 68
char = (;code = 40
char = 3;code = 51
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = D;code = 68
char = A;code = 65
char = -;code = 45
char = M;code = 77
char = B;code = 66
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result sql = 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the most active vitamin D metabolite, regulates proliferation, survival, and differentiation in many cell types. 1,25(OH)(2)D(3) and several less calcemic analogs are in clinical trials against various neoplasias. We studied the effects of 1,25(OH)(2)D(3) on a panel of human breast cancer cells, which show similar vitamin D receptor (VDR) content but variable transcriptional and anti-proliferative responsiveness. In MDA-MB-453 cells, one of the responsive lines, 1,25(OH)(2)D(3) increased cell and nuclear size and induced a change from a rounded to a flattened morphology. By phase contrast, laser confocal and electron microscopy, we found that 1,25(OH)(2)D(3) changed the cytoarchitecture of actin filaments and microtubules and nuclear shape, induced filopodia and lamellipodia, and promoted cell-to-cell contacts via large cytoplasmic extensions. However, although claudin-7 and occludin content in the cells increased upon exposure to 1,25(OH)(2)D(3), these proteins were not located at the plasma membrane probably due to the absence of E-cadherin expression. Additionally, 1,25(OH)(2)D(3) induced the accumulation of alpha(v)-integrin, beta(5)-integrin, focal adhesion kinase (FAK), and paxillin in focal adhesion plaques, concomitant with the increased phosphorylation of the FAK. 1,25(OH)(2)D(3) enhanced MDA-MB-453 and MDA-MB-468 cell adhesion to plastic but decreased adhesion to laminin. The expression of the mesenchymal marker N-cadherin and of the myoepithelial marker P-cadherin was down-regulated by 1,25(OH)(2)D(3) in several breast cancer cell lines. Other myoepithelial proteins such as alpha(6)-integrin, beta(4)-integrin, and smooth muscle alpha-actin (SMA) were also repressed by 1,25(OH)(2)D(3) in MDA-MB-453 and MDA-MB-468 cells. Accordingly, mice lacking VDR (Vdr(-/-)) showed abnormally high levels of SMA and P-cadherin in their mammary gland. These findings show that 1,25(OH)(2)D(3) profoundly affects the phenotype of breast cancer cells, and suggest that it reverts the myoepithelial features associated with more aggressive forms and poor prognosis in human breast cancer.

Publication: Differentiation 2007 Mar ;75(3)::193-207.
Publication Date: 2007 Mar
Study Author(s): Pendás-Franco, Natalia;González-Sancho, José Manuel;Suárez, Yajaira;Aguilera, Oscar;Steinmeyer, Andreas;Gamallo, Carlos;Berciano, María T;Lafarga, Miguel;Muñoz, Alberto;
Institution: Instituto de Investigaciones Biomédicas Alberto Sols Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid E-28029 Madrid, Spain.
Shortcut link to this study:
1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the most active vitamin D metabolite, regulates proliferation, survival, and differentiation in many cell types. 1,25(OH)(2)D(3) and several less calcemic analogs are in clinical trials against various neoplasias. We studied the effects of 1,25(OH)(2)D(3) on a panel of human breast cancer cells, which show similar vitamin D receptor (VDR) content but variable transcriptional and anti-proliferative responsiveness. In MDA-MB-453 cells, one of the responsive lines, 1,25(OH)(2)D(3) increased cell and nuclear size and induced a change from a rounded to a flattened morphology. By phase contrast, laser confocal and electron microscopy, we found that 1,25(OH)(2)D(3) changed the cytoarchitecture of actin filaments and microtubules and nuclear shape, induced filopodia and lamellipodia, and promoted cell-to-cell contacts via large cytoplasmic extensions. However, although claudin-7 and occludin content in the cells increased upon exposure to 1,25(OH)(2)D(3), these proteins were not located at the plasma membrane probably due to the absence of E-cadherin expression. Additionally, 1,25(OH)(2)D(3) induced the accumulation of alpha(v)-integrin, beta(5)-integrin, focal adhesion kinase (FAK), and paxillin in focal adhesion plaques, concomitant with the increased phosphorylation of the FAK. 1,25(OH)(2)D(3) enhanced MDA-MB-453 and MDA-MB-468 cell adhesion to plastic but decreased adhesion to laminin. The expression of the mesenchymal marker N-cadherin and of the myoepithelial marker P-cadherin was down-regulated by 1,25(OH)(2)D(3) in several breast cancer cell lines. Other myoepithelial proteins such as alpha(6)-integrin, beta(4)-integrin, and smooth muscle alpha-actin (SMA) were also repressed by 1,25(OH)(2)D(3) in MDA-MB-453 and MDA-MB-468 cells. Accordingly, mice lacking VDR (Vdr(-/-)) showed abnormally high levels of SMA and P-cadherin in their mammary gland. These findings show that 1,25(OH)(2)D(3) profoundly affects the phenotype of breast cancer cells, and suggest that it reverts the myoepithelial features associated with more aggressive forms and poor prognosis in human breast cancer.
PMID: 17288543

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