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char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
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char = n;code = 110
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char = w;code = 119
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char = l;code = 108
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char = p;code = 112
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
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char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 5;code = 53
char = 3;code = 51
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 = 32
char = e;code = 101
char = p;code = 112
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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
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char = b;code = 98
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = p;code = 112
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = .;code = 46
result sql = Differential regulation of signal transduction pathways in wild type and mutated p53 breast cancer epithelial cells by copper and zinc.
Differential regulation of signal transduction pathways in wild type and mutated p53 breast cancer epithelial cells by copper and zinc.
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char = g;code = 103
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char = s;code = 115
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char = T;code = 84
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char = s;code = 115
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char = f;code = 102
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char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = /;code = 47
char = A;code = 65
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result sql = Previous studies have suggested that cells may differ in their response to metal stress. This study was undertaken to investigate the role of PI3K/Akt signaling pathway in metal resistance in human breast cancer epithelial cells with different p53 and estrogen receptor status. Exposure to copper and zinc increased Akt phosphorylation with its nuclear localization only in MDA-MB-231 cells with no estrogen receptor and mutated p53. Cyclin D1 expression and cell-cycle progression followed the metal-induced Akt phosphorylation. Treatment with LY294002 abrogated these effects, suggesting the essential role of PI3-kinase. In contrast, in MCF-7 cells with wild type p53 and estrogen receptor, there was no change in Akt activation, while suppression of p53 activity by pifithrin-alpha increased phosphorylation of Akt after the treatment with copper. In MCF-7 cells, the metal treatment increased the phosphorylation of p53 at serine 15, up-regulated p21 expression, and resulted in cell-cycle arrest in G1 phase with apoptosis. These results demonstrate that copper-induced apoptosis in MCF-7 cells is p53 dependent, whereas the metal resistance in MDA-MB-231 cells may be due to activation of Akt in the absence of a functional p53.

Publication: Arch. Biochem. Biophys. 2004 Mar 15 ;423(2)::351-61.
Publication Date: 2004 Mar 15
Study Author(s): Ostrakhovitch, E A;Cherian, M G;
Institution: Department of Pathology, University of Western Ontario, London, Ont., Canada N6A5C1. [email protected]
Shortcut link to this study:
Previous studies have suggested that cells may differ in their response to metal stress. This study was undertaken to investigate the role of PI3K/Akt signaling pathway in metal resistance in human breast cancer epithelial cells with different p53 and estrogen receptor status. Exposure to copper and zinc increased Akt phosphorylation with its nuclear localization only in MDA-MB-231 cells with no estrogen receptor and mutated p53. Cyclin D1 expression and cell-cycle progression followed the metal-induced Akt phosphorylation. Treatment with LY294002 abrogated these effects, suggesting the essential role of PI3-kinase. In contrast, in MCF-7 cells with wild type p53 and estrogen receptor, there was no change in Akt activation, while suppression of p53 activity by pifithrin-alpha increased phosphorylation of Akt after the treatment with copper. In MCF-7 cells, the metal treatment increased the phosphorylation of p53 at serine 15, up-regulated p21 expression, and resulted in cell-cycle arrest in G1 phase with apoptosis. These results demonstrate that copper-induced apoptosis in MCF-7 cells is p53 dependent, whereas the metal resistance in MDA-MB-231 cells may be due to activation of Akt in the absence of a functional p53.
PMID: 15001399

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