|
|
char = I;code = 73
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char = I;code = 73
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char = M;code = 77
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char = b;code = 98
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char = t;code = 116
char = ;code = 32
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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 = s;code = 115
char = :;code = 58
char = ;code = 32
char = A;code = 65
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char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
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char = k;code = 107
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char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
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char = h;code = 104
char = ;code = 32
char = f;code = 102
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char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = i;code = 105
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char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = 46
result sql = Inhibition of insulin-like growth factor I receptor signaling by the vitamin D analogue EB1089 in MCF-7 breast cancer cells: A role for insulin-like growth factor binding proteins.
Inhibition of insulin-like growth factor I receptor signaling by the vitamin D analogue EB1089 in MCF-7 breast cancer cells: A role for insulin-like growth factor binding proteins.char = I;code = 73
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char = u;code = 117
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char = i;code = 105
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char = i;code = 105
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
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char = h;code = 104
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char = f;code = 102
char = a;code = 97
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char = ;code = 32
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char = ;code = 32
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char = I;code = 73
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char = G;code = 71
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char = I;code = 73
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char = i;code = 105
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char = b;code = 98
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char = W;code = 87
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result sql = Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens involved in growth regulation of breast epithelial cells and are implicated in the pathophysiology of breast cancer. Their bioactivity is enhanced or inhibited by specific IGF-binding proteins (IGFBPs). Vitamin D-related compounds (VDRCs) have been shown to inhibit proliferation and induce apoptosis of MCF-7 breast carcinoma cells. We have previously demonstrated that VDRCs antagonize the growth-promoting activity of IGF-I by stimulating autocrine production of IGFBP-5 in MCF-7 cells, but the effect of VDRCs on IGF-I receptor (IGF-IR) intracellular signaling has not been elucidated. We report here that the vitamin D analogue EB1089 interferes with the IGF-IR signaling pathway by attenuating IGF-I-induced tyrosine phosphorylation of IRS-1, and to a lesser extent, IRS-2. It does not affect protein levels of IRS-1, IRS-2 or IGF-IR. However, EB1089 does not inhibit tyrosine phosphorylation of IRS-1 induced by des(1-3) IGF-I, an IGF-I analogue with greatly reduced affinity for IGFBPs. Furthermore, we demonstrate that an antisense IGFBP-5 oligodeoxynucleotide attenuates EB1089-induced inhibition of IGF-I-stimulated tyrosine phosphorylation of IRS-1 and EB1089-induced IGFBP-5 accumulation. These data strongly suggest that IGFBP-5 plays a functional role in the interfering action of EB1089 with the IGF-IR signal transduction pathway.
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result sql = Inhibition of insulin-like growth factor I receptor signaling by the vitamin D analogue EB1089 in MCF-7 breast cancer cells: A role for insulin-like growth factor binding proteins.
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char = i;code = 105
char = k;code = 107
char = e;code = 101
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 = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = I;code = 73
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = I;code = 73
char = I;code = 73
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
char = I;code = 73
char = );code = 41
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = s;code = 115
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 = 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 = 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 = 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 = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = p;code = 112
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
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 = p;code = 112
char = h;code = 104
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
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
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = s;code = 115
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 = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = (;code = 40
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = B;code = 66
char = P;code = 80
char = s;code = 115
char = );code = 41
char = .;code = 46
char = ;code = 32
char = V;code = 86
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = V;code = 86
char = D;code = 68
char = R;code = 82
char = C;code = 67
char = s;code = 115
char = );code = 41
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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 = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = a;code = 97
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 = 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 = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
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 = a;code = 97
char = t;code = 116
char = ;code = 32
char = V;code = 86
char = D;code = 68
char = R;code = 82
char = C;code = 67
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = 45
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
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 = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = B;code = 66
char = P;code = 80
char = -;code = 45
char = 5;code = 53
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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 = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
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 = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = V;code = 86
char = D;code = 68
char = R;code = 82
char = C;code = 67
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
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 = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
char = R;code = 82
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
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 = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = W;code = 87
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 = ;code = 32
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = v;code = 118
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = B;code = 66
char = 1;code = 49
char = 0;code = 48
char = 8;code = 56
char = 9;code = 57
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = s;code = 115
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
char = ;code = 32
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
char = R;code = 82
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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = u;code = 117
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 = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
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 = t;code = 116
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = S;code = 83
char = -;code = 45
char = 1;code = 49
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 = o;code = 111
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = S;code = 83
char = -;code = 45
char = 2;code = 50
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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 = ;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
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = S;code = 83
char = -;code = 45
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = I;code = 73
char = R;code = 82
char = S;code = 83
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = I;code = 73
char = R;code = 82
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 = E;code = 69
char = B;code = 66
char = 1;code = 49
char = 0;code = 48
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result sql = Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens involved in growth regulation of breast epithelial cells and are implicated in the pathophysiology of breast cancer. Their bioactivity is enhanced or inhibited by specific IGF-binding proteins (IGFBPs). Vitamin D-related compounds (VDRCs) have been shown to inhibit proliferation and induce apoptosis of MCF-7 breast carcinoma cells. We have previously demonstrated that VDRCs antagonize the growth-promoting activity of IGF-I by stimulating autocrine production of IGFBP-5 in MCF-7 cells, but the effect of VDRCs on IGF-I receptor (IGF-IR) intracellular signaling has not been elucidated. We report here that the vitamin D analogue EB1089 interferes with the IGF-IR signaling pathway by attenuating IGF-I-induced tyrosine phosphorylation of IRS-1, and to a lesser extent, IRS-2. It does not affect protein levels of IRS-1, IRS-2 or IGF-IR. However, EB1089 does not inhibit tyrosine phosphorylation of IRS-1 induced by des(1-3) IGF-I, an IGF-I analogue with greatly reduced affinity for IGFBPs. Furthermore, we demonstrate that an antisense IGFBP-5 oligodeoxynucleotide attenuates EB1089-induced inhibition of IGF-I-stimulated tyrosine phosphorylation of IRS-1 and EB1089-induced IGFBP-5 accumulation. These data strongly suggest that IGFBP-5 plays a functional role in the interfering action of EB1089 with the IGF-IR signal transduction pathway.
Publication: Int. J. Oncol. 1999 Sep ;15(3)::589-94.
Publication Date: 1999 Sep
Study Author(s): Rozen, F;Pollak, M;
Institution: Lady Davis Institute for Medical Research of the Jewish General Hospital and Departments of Medicine and Oncology, McGill University, Montreal, Quebec H3T 1E2, Canada.
Shortcut link to this study:
Publication Date: 1999 Sep
Study Author(s): Rozen, F;Pollak, M;
Institution: Lady Davis Institute for Medical Research of the Jewish General Hospital and Departments of Medicine and Oncology, McGill University, Montreal, Quebec H3T 1E2, Canada.
Shortcut link to this study:
Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens involved in growth regulation of breast epithelial cells and are implicated in the pathophysiology of breast cancer. Their bioactivity is enhanced or inhibited by specific IGF-binding proteins (IGFBPs). Vitamin D-related compounds (VDRCs) have been shown to inhibit proliferation and induce apoptosis of MCF-7 breast carcinoma cells. We have previously demonstrated that VDRCs antagonize the growth-promoting activity of IGF-I by stimulating autocrine production of IGFBP-5 in MCF-7 cells, but the effect of VDRCs on IGF-I receptor (IGF-IR) intracellular signaling has not been elucidated. We report here that the vitamin D analogue EB1089 interferes with the IGF-IR signaling pathway by attenuating IGF-I-induced tyrosine phosphorylation of IRS-1, and to a lesser extent, IRS-2. It does not affect protein levels of IRS-1, IRS-2 or IGF-IR. However, EB1089 does not inhibit tyrosine phosphorylation of IRS-1 induced by des(1-3) IGF-I, an IGF-I analogue with greatly reduced affinity for IGFBPs. Furthermore, we demonstrate that an antisense IGFBP-5 oligodeoxynucleotide attenuates EB1089-induced inhibition of IGF-I-stimulated tyrosine phosphorylation of IRS-1 and EB1089-induced IGFBP-5 accumulation. These data strongly suggest that IGFBP-5 plays a functional role in the interfering action of EB1089 with the IGF-IR signal transduction pathway.
PMID: 10427145
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