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char = s;code = 115
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char = c;code = 99
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char = 2;code = 50
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char = a;code = 97
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char = e;code = 101
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char = e;code = 101
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char = a;code = 97
char = s;code = 115
char = t;code = 116
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char = c;code = 99
char = a;code = 97
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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 = 46
result sql = Expression of cyclooxygenase-2 is regulated by glycogen synthase kinase-3beta in gastric cancer cells.
Expression of cyclooxygenase-2 is regulated by glycogen synthase kinase-3beta in gastric cancer cells.
char = C;code = 67
char = y;code = 121
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char = y;code = 121
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char = e;code = 101
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char = e;code = 101
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = O;code = 79
char = X;code = 88
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char = 2;code = 50
char = );code = 41
char = ;code = 32
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char = n;code = 110
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char = i;code = 105
char = s;code = 115
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char = a;code = 97
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char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
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char = r;code = 114
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = o;code = 111
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char = r;code = 114
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char = o;code = 111
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char = i;code = 105
char = s;code = 115
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char = i;code = 105
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char = g;code = 103
char = a;code = 97
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char = c;code = 99
char = ;code = 32
char = c;code = 99
char = a;code = 97
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char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
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char = t;code = 116
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char = e;code = 101
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char = c;code = 99
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char = m;code = 109
char = o;code = 111
char = r;code = 114
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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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
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char = r;code = 114
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = n;code = 110
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = i;code = 105
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char = a;code = 97
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char = ;code = 32
char = m;code = 109
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char = e;code = 101
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char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
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char = m;code = 109
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char = ;code = 32
char = t;code = 116
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char = a;code = 97
char = t;code = 116
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char = l;code = 108
char = e;code = 101
char = a;code = 97
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = C;code = 67
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 2;code = 50
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char = o;code = 111
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char = s;code = 115
char = i;code = 105
char = o;code = 111
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char = i;code = 105
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char = t;code = 116
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char = s;code = 115
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char = W;code = 87
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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 = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
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char = ;code = 32
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char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = i;code = 105
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char = i;code = 105
char = b;code = 98
char = i;code = 105
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = d;code = 100
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char = i;code = 105
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char = o;code = 111
char = l;code = 108
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char = 3;code = 51
char = -;code = 45
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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = L;code = 76
char = Y;code = 89
char = 2;code = 50
char = 9;code = 57
char = 4;code = 52
char = 0;code = 48
char = 0;code = 48
char = 2;code = 50
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char = s;code = 115
char = u;code = 117
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char = p;code = 112
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = b;code = 98
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char = a;code = 97
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char = ;code = 32
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char = h;code = 104
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char = b;code = 98
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char = ;code = 32
char = m;code = 109
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char = r;code = 114
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char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = c;code = 99
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char = a;code = 97
char = t;code = 116
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char = d;code = 100
char = u;code = 117
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char = d;code = 100
char = ;code = 32
char = C;code = 67
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 2;code = 50
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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 = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = T;code = 84
char = M;code = 77
char = K;code = 75
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char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = M;code = 77
char = K;code = 75
char = N;code = 78
char = -;code = 45
char = 2;code = 50
char = 8;code = 56
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = r;code = 114
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char = c;code = 99
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char = c;code = 99
char = a;code = 97
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char = c;code = 99
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 = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
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char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = o;code = 111
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char = i;code = 105
char = b;code = 98
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char = a;code = 97
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char = G;code = 71
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char = );code = 41
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char = S;code = 83
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char = 4;code = 52
char = 1;code = 49
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char = o;code = 111
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char = C;code = 67
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char = m;code = 109
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char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
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char = l;code = 108
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char = a;code = 97
char = s;code = 115
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char = e;code = 101
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char = e;code = 101
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char = 4;code = 52
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char = d;code = 100
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char = a;code = 97
char = l;code = 108
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char = G;code = 71
char = S;code = 83
char = K;code = 75
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char = 3;code = 51
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result sql = Cyclooxygenase-2 (COX-2) expression is a marker of poor prognosis in gastric cancer patients, and its inhibition suppresses gastric tumorigenesis in experimental animal models. The mechanism that leads to COX-2 overexpression in this tumor type is unknown. We have now shown that inhibition of phosphatidylinositol 3-kinase by LY294002 suppresses both basal and phorbol myristate acetate-induced COX-2 expression in TMK-1 and MKN-28 gastric cancer cells. Furthermore, inhibition of glycogen synthase kinase-3beta (GSK-3beta) by SB415286 induced expression of COX-2 mRNA and protein as well as the enzyme activity in the gastric cancer cells. The effect of SB415286 was confirmed by the use of two additional GSK-3beta inhibitors, lithium chloride and SB216763. SB415286 had a modest 1.6-fold stimulatory effect on a 2-kb COX-2 promoter reporter construct, but more importantly, it was shown to block the decay of COX-2 mRNA. In contrast to modulation of phosphatidylinositol 3-kinase/Akt/GSK-3beta pathway, inhibitors of mitogen-activated protein kinases (MEK 1/2, p38, JNK) or the mammalian target of rapamycin did not alter COX-2 expression in gastric cancer cells. Our data show that inhibition of GSK-3beta stimulates COX-2 expression in gastric cancer cells, which seems to be primarily facilitated via an increase in mRNA stability and to a lesser extent through enhanced transcription.

Publication: J. Biol. Chem. 2006 Feb 24 ;281(8)::4564-9.
Publication Date: 2006 Feb 24
Study Author(s): Thiel, Alexandra;Heinonen, Mira;Rintahaka, Johanna;Hallikainen, Tuija;Hemmes, Annabrita;Dixon, Dan A;Haglund, Caj;Ristimäki, Ari;
Institution: Department of Pathology, Helsinki University Central Hospital, and Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
Shortcut link to this study:
Cyclooxygenase-2 (COX-2) expression is a marker of poor prognosis in gastric cancer patients, and its inhibition suppresses gastric tumorigenesis in experimental animal models. The mechanism that leads to COX-2 overexpression in this tumor type is unknown. We have now shown that inhibition of phosphatidylinositol 3-kinase by LY294002 suppresses both basal and phorbol myristate acetate-induced COX-2 expression in TMK-1 and MKN-28 gastric cancer cells. Furthermore, inhibition of glycogen synthase kinase-3beta (GSK-3beta) by SB415286 induced expression of COX-2 mRNA and protein as well as the enzyme activity in the gastric cancer cells. The effect of SB415286 was confirmed by the use of two additional GSK-3beta inhibitors, lithium chloride and SB216763. SB415286 had a modest 1.6-fold stimulatory effect on a 2-kb COX-2 promoter reporter construct, but more importantly, it was shown to block the decay of COX-2 mRNA. In contrast to modulation of phosphatidylinositol 3-kinase/Akt/GSK-3beta pathway, inhibitors of mitogen-activated protein kinases (MEK 1/2, p38, JNK) or the mammalian target of rapamycin did not alter COX-2 expression in gastric cancer cells. Our data show that inhibition of GSK-3beta stimulates COX-2 expression in gastric cancer cells, which seems to be primarily facilitated via an increase in mRNA stability and to a lesser extent through enhanced transcription.
PMID: 16371352

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