|
|
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result sql = Glycogen synthase kinase-3beta participates in nuclear factor kappaB-mediated gene transcription and cell survival in pancreatic cancer cells.
Glycogen synthase kinase-3beta participates in nuclear factor kappaB-mediated gene transcription and cell survival in pancreatic cancer cells.char = R;code = 82
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char = G;code = 71
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result sql = Recent studies using glycogen synthase kinase-3beta (GSK-3beta)-deficient mouse embryonic fibroblasts suggest that GSK-3beta positively regulates nuclear factor kappaB (NFkappaB)-mediated gene transcription. Because NFkappaB is suggested to participate in cell proliferation and survival pathways in pancreatic cancer, we investigated the role of GSK-3beta in regulating these cellular processes. Herein, we show that pancreatic cancer cells contain a pool of active GSK-3beta and that pharmacologic inhibition of GSK-3 kinase activity using small molecule inhibitors or genetic depletion of GSK-3beta by RNA interference leads to decreased cancer cell proliferation and survival. Mechanistically, we show that GSK-3beta influences NFkappaB-mediated gene transcription at a point distal to the Ikappa kinase complex, as only ectopic expression of the NFkappaB subunits p65/p50, but not an Ikappa kinase beta constitutively active mutant, could rescue the decreased cellular proliferation and survival associated with GSK-3beta inhibition. Taken together, our results simultaneously identify a previously unrecognized role for GSK-3beta in cancer cell survival and proliferation and suggest GSK-3beta as a potential therapeutic target in the treatment of pancreatic cancer.
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result sql = Glycogen synthase kinase-3beta participates in nuclear factor kappaB-mediated gene transcription and cell survival in pancreatic cancer cells.
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char = c;code = 99
char = i;code = 105
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = i;code = 105
char = n;code = 110
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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 = 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
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char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
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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 = s;code = 115
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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 = 44
char = ;code = 32
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
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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 = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = K;code = 75
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char = 3;code = 51
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = i;code = 105
char = n;code = 110
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 = n;code = 110
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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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 = 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 = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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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
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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 = c;code = 99
char = o;code = 111
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char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = K;code = 75
char = -;code = 45
char = 3;code = 51
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
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 = a;code = 97
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = c;code = 99
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 = 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 = G;code = 71
char = S;code = 83
char = K;code = 75
char = -;code = 45
char = 3;code = 51
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
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
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char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = e;code = 101
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 = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = d;code = 100
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = e;code = 101
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 = G;code = 71
char = S;code = 83
char = K;code = 75
char = -;code = 45
char = 3;code = 51
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
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
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = e;code = 101
char = a;code = 97
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char = s;code = 115
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char = t;code = 116
char = o;code = 111
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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
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char = c;code = 99
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char = c;code = 99
char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
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char = o;code = 111
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char = i;code = 105
char = f;code = 102
char = e;code = 101
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char = a;code = 97
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char = o;code = 111
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char = a;code = 97
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char = d;code = 100
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char = s;code = 115
char = u;code = 117
char = r;code = 114
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char = v;code = 118
char = a;code = 97
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char = .;code = 46
char = ;code = 32
char = M;code = 77
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = s;code = 115
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char = i;code = 105
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char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
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char = e;code = 101
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char = h;code = 104
char = o;code = 111
char = w;code = 119
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = K;code = 75
char = -;code = 45
char = 3;code = 51
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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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 = 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
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
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char = s;code = 115
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char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = I;code = 73
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = k;code = 107
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char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = c;code = 99
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char = p;code = 112
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char = e;code = 101
char = x;code = 120
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
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char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
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char = e;code = 101
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = c;code = 99
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = u;code = 117
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = s;code = 115
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char = p;code = 112
char = 6;code = 54
char = 5;code = 53
char = /;code = 47
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char = 5;code = 53
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char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
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char = n;code = 110
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char = t;code = 116
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char = a;code = 97
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char = I;code = 73
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = k;code = 107
char = i;code = 105
char = n;code = 110
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char = s;code = 115
char = e;code = 101
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char = a;code = 97
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char = c;code = 99
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char = u;code = 117
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = u;code = 117
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char = a;code = 97
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char = o;code = 111
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char = f;code = 102
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char = o;code = 111
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char = r;code = 114
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char = a;code = 97
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char = e;code = 101
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = K;code = 75
char = -;code = 45
char = 3;code = 51
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = a;code = 97
char = k;code = 107
char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ,;code = 44
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char = a;code = 97
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char = s;code = 115
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char = y;code = 121
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char = e;code = 101
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char = t;code = 116
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char = f;code = 102
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char = a;code = 97
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char = p;code = 112
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char = e;code = 101
char = v;code = 118
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char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
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char = r;code = 114
char = e;code = 101
char = c;code = 99
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char = i;code = 105
char = z;code = 122
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char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = K;code = 75
char = -;code = 45
char = 3;code = 51
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = i;code = 105
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char = c;code = 99
char = a;code = 97
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char = e;code = 101
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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 = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
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result sql = Recent studies using glycogen synthase kinase-3beta (GSK-3beta)-deficient mouse embryonic fibroblasts suggest that GSK-3beta positively regulates nuclear factor kappaB (NFkappaB)-mediated gene transcription. Because NFkappaB is suggested to participate in cell proliferation and survival pathways in pancreatic cancer, we investigated the role of GSK-3beta in regulating these cellular processes. Herein, we show that pancreatic cancer cells contain a pool of active GSK-3beta and that pharmacologic inhibition of GSK-3 kinase activity using small molecule inhibitors or genetic depletion of GSK-3beta by RNA interference leads to decreased cancer cell proliferation and survival. Mechanistically, we show that GSK-3beta influences NFkappaB-mediated gene transcription at a point distal to the Ikappa kinase complex, as only ectopic expression of the NFkappaB subunits p65/p50, but not an Ikappa kinase beta constitutively active mutant, could rescue the decreased cellular proliferation and survival associated with GSK-3beta inhibition. Taken together, our results simultaneously identify a previously unrecognized role for GSK-3beta in cancer cell survival and proliferation and suggest GSK-3beta as a potential therapeutic target in the treatment of pancreatic cancer.
Publication: Cancer Res. 2005 Mar 15 ;65(6)::2076-81.
Publication Date: 2005 Mar 15
Study Author(s): Ougolkov, Andrei V;Fernandez-Zapico, Martin E;Savoy, Doris N;Urrutia, Raul A;Billadeau, Daniel D;
Institution: Division of Oncology Research and GI Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
Shortcut link to this study:
Publication Date: 2005 Mar 15
Study Author(s): Ougolkov, Andrei V;Fernandez-Zapico, Martin E;Savoy, Doris N;Urrutia, Raul A;Billadeau, Daniel D;
Institution: Division of Oncology Research and GI Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
Shortcut link to this study:
Recent studies using glycogen synthase kinase-3beta (GSK-3beta)-deficient mouse embryonic fibroblasts suggest that GSK-3beta positively regulates nuclear factor kappaB (NFkappaB)-mediated gene transcription. Because NFkappaB is suggested to participate in cell proliferation and survival pathways in pancreatic cancer, we investigated the role of GSK-3beta in regulating these cellular processes. Herein, we show that pancreatic cancer cells contain a pool of active GSK-3beta and that pharmacologic inhibition of GSK-3 kinase activity using small molecule inhibitors or genetic depletion of GSK-3beta by RNA interference leads to decreased cancer cell proliferation and survival. Mechanistically, we show that GSK-3beta influences NFkappaB-mediated gene transcription at a point distal to the Ikappa kinase complex, as only ectopic expression of the NFkappaB subunits p65/p50, but not an Ikappa kinase beta constitutively active mutant, could rescue the decreased cellular proliferation and survival associated with GSK-3beta inhibition. Taken together, our results simultaneously identify a previously unrecognized role for GSK-3beta in cancer cell survival and proliferation and suggest GSK-3beta as a potential therapeutic target in the treatment of pancreatic cancer.
PMID: 15781615
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