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result sql = Extracellular calcium downregulates estrogen receptor alpha and increases its transcriptional activity through calcium-sensing receptor in breast cancer cells.

Extracellular calcium downregulates estrogen receptor alpha and increases its transcriptional activity through calcium-sensing receptor in breast cancer cells.

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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = E;code = 69
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
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 = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
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char = .;code = 46
char = ;code = 32
char = M;code = 77
char = o;code = 111
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char = e;code = 101
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
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char = ;code = 32
char = 3;code = 51
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = 2;code = 50
char = +;code = 43
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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
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char = o;code = 111
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = g;code = 103
char = R;code = 82
char = );code = 41
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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = 4;code = 52
char = 5;code = 53
char = ;code = 32
char = +;code = 43
char = /;code = 47
char = -;code = 45
char = ;code = 32
char = 8;code = 56
char = %;code = 37
char = .;code = 46
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char = M;code = 77
char = g;code = 103
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char = t;code = 116
char = e;code = 101
char = s;code = 115
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char = e;code = 101
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char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = 2;code = 50
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char = ;code = 32
char = m;code = 109
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char = d;code = 100
char = i;code = 105
char = d;code = 100
char = ;code = 32
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char = o;code = 111
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char = ;code = 32
char = e;code = 101
char = x;code = 120
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
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char = 1;code = 49
char = 7;code = 55
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = -;code = 45
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ;code = 32
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
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
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 = 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 = r;code = 114
char = e;code = 101
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 = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = P;code = 80
char = g;code = 103
char = R;code = 82
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 = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = C;code = 67
char = I;code = 73
char = ;code = 32
char = 1;code = 49
char = 8;code = 56
char = 2;code = 50
char = ,;code = 44
char = 7;code = 55
char = 8;code = 56
char = 0;code = 48
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = a;code = 97
char = b;code = 98
char = r;code = 114
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char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = a;code = 97
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char = i;code = 105
char = v;code = 118
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 = t;code = 116
char = h;code = 104
char = e;code = 101
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char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = g;code = 103
char = e;code = 101
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char = e;code = 101
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = i;code = 105
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char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = P;code = 80
char = g;code = 103
char = R;code = 82
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
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char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
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char = b;code = 98
char = y;code = 121
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char = C;code = 67
char = a;code = 97
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char = ,;code = 44
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char = i;code = 105
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char = t;code = 116
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char = a;code = 97
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char = C;code = 67
char = a;code = 97
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char = +;code = 43
char = ;code = 32
char = m;code = 109
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char = e;code = 101
char = x;code = 120
char = e;code = 101
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char = a;code = 97
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char = w;code = 119
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char = a;code = 97
char = k;code = 107
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char = a;code = 97
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char = d;code = 100
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char = e;code = 101
char = c;code = 99
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char = f;code = 102
char = i;code = 105
char = c;code = 99
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char = r;code = 114
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char = e;code = 101
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char = i;code = 105
char = c;code = 99
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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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 = ;code = 32
char = C;code = 67
char = a;code = 97
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = R;code = 82
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
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char = h;code = 104
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char = c;code = 99
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char = l;code = 108
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char = m;code = 109
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char = e;code = 101
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char = l;code = 108
char = a;code = 97
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char = e;code = 101
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char = C;code = 67
char = a;code = 97
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char = +;code = 43
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char = i;code = 105
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char = f;code = 102
char = l;code = 108
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char = c;code = 99
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char = d;code = 100
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char = h;code = 104
char = e;code = 101
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char = o;code = 111
char = p;code = 112
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char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = A;code = 65
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char = 3;code = 51
char = 1;code = 49
char = 8;code = 56
char = 7;code = 55
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char = f;code = 102
char = a;code = 97
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char = l;code = 108
char = e;code = 101
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char = a;code = 97
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char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = E;code = 69
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
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char = h;code = 104
char = a;code = 97
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char = e;code = 101
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char = u;code = 117
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char = e;code = 101
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char = C;code = 67
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 = e;code = 101
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char = i;code = 105
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char = M;code = 77
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char = c;code = 99
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char = W;code = 87
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char = f;code = 102
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char = r;code = 114
char = s;code = 115
char = t;code = 116
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char = e;code = 101
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char = f;code = 102
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = a;code = 97
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char = .;code = 46
char = ;code = 32
char = E;code = 69
char = x;code = 120
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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
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char = 1;code = 49
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char = m;code = 109
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char = c;code = 99
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char = N;code = 78
char = P;code = 80
char = S;code = 83
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char = R;code = 82
char = -;code = 45
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char = 6;code = 54
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char = e;code = 101
char = d;code = 100
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char = w;code = 119
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char = ;code = 32
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char = t;code = 116
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char = o;code = 111
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char = n;code = 110
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = o;code = 111
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char = R;code = 82
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char = s;code = 115
char = ;code = 32
char = w;code = 119
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char = v;code = 118
char = a;code = 97
char = t;code = 116
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char = ;code = 32
char = t;code = 116
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char = e;code = 101
char = ;code = 32
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char = e;code = 101
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 = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = (;code = 40
char = 2;code = 50
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char = );code = 41
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char = ;code = 32
char = r;code = 114
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char = t;code = 116
char = s;code = 115
char = ;code = 32
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char = g;code = 103
char = g;code = 103
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char = t;code = 116
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char = l;code = 108
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char = l;code = 108
char = a;code = 97
char = r;code = 114
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char = C;code = 67
char = a;code = 97
char = 2;code = 50
char = +;code = 43
char = ;code = 32
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char = n;code = 110
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = ;code = 32
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
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char = m;code = 109
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char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = ;code = 32
char = a;code = 97
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char = ;code = 32
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char = a;code = 97
char = s;code = 115
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char = ;code = 32
char = i;code = 105
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char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
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char = ;code = 32
char = m;code = 109
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char = d;code = 100
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = k;code = 107
char = e;code = 101
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
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char = e;code = 101
char = a;code = 97
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char = t;code = 116
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
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
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char = t;code = 116
char = h;code = 104
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char = d;code = 100
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = e;code = 101
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 = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = -;code = 45
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 = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
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result sql = Skeleton is the most common organ targeted by breast cancer cells, especially from estrogen receptor alpha (ER)-positive neoplasms. Metastatic cells can stimulate directly or indirectly osteoclast-mediated bone resorption. Tumor-induced osteolysis is often extensive and leads to the release of large quantities of calcium. Metastatic cancer cells can be thus exposed to high calcium concentrations (40 mM has been reported at the resorption site). However, the effects of Ca2+ on breast cancer cells have been minimally examined. We showed that 20-mM extracellular Ca2+ induced a downregulation of ER protein in MCF-7 cells and caused ER-mediated transactivation of a reporter gene by 55 +/- 10% (mean +/- SD) in MVLN cells (MCF-7 cells stably transfected with ERE and luciferase reporter gene). Moreover, 3 mM Ca2+ increased progesterone receptor (PgR) expression by 45 +/- 8%. Mg2+ tested at up to 20 mM did not exert any effects, while 17beta-estradiol downregulated ER, transactivated the reporter gene, and enhanced PgR expression. The pure antiestrogen ICI 182,780 was able to abrogate the transactivation of the reporter gene and the increase in PgR levels induced by Ca2+, indicating that Ca2+ may exert a weak and specific estrogenic effect in MCF-7 cells. Ca2+ effects on ER probably start at the cell membrane level since a large Ca2+ influx caused by the ionophore A23187 failed to activate ER. We have thus studied the involvement of the membrane calcium-sensing receptor (CaR) that is known to be expressed notably in MCF-7 cells. We first tested the effects of a specific activator of CaR. Exposure to 10(-4) M calcimimetic NPS R-467 mirrored the changes observed with extracellular Ca2+ by inducing a marked decrease in ER protein levels, increasing the transcriptional activity of ER (67 +/- 12%) and stimulating PgR expression (41 +/- 4%). As expected, the NPS S-467 isomer was less effective. Furthermore, a highly selective CaR antagonist partly suppressed the downregulation of ER as well as transactivation of the reporter gene induced by Ca(2+). Our results suggest that the effects of extracellular Ca2+ on ER expression and activity are mediated, at least in part, by the CaR. In summary, calcium released during the process of metastatic bone destruction could modulate the functions of the estrogen receptor, a key receptor involved in breast cancer cells growth and function, and thus participate in the pathogenesis of tumor-induced osteolysis.

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