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result sql = Direct gene transfer of adenoviral-mediated interferon α into human bladder cancer cells but not the bystander factors produced induces endoplasmic reticulum stress-related cytotoxicity.
Direct gene transfer of adenoviral-mediated interferon α into human bladder cancer cells but not the bystander factors produced induces endoplasmic reticulum stress-related cytotoxicity.
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char = i;code = 105
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = v;code = 118
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char = r;code = 114
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char = l;code = 108
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char = a;code = 97
char = d;code = 100
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char = c;code = 99
char = o;code = 111
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char = d;code = 100
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char = b;code = 98
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
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char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
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char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = r;code = 114
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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 = ;code = 32
char = d;code = 100
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
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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 = s;code = 115
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char = i;code = 105
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char = f;code = 102
char = e;code = 101
char = c;code = 99
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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 = t;code = 116
char = h;code = 104
char = ;code = 32
char = A;code = 65
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char = I;code = 73
char = F;code = 70
char = N;code = 78
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char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 5;code = 53
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char = ;code = 32
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char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
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
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
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
char = s;code = 115
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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 = b;code = 98
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
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char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
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char = r;code = 114
char = s;code = 115
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 = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
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
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
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char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = d;code = 100
char = -;code = 45
char = I;code = 73
char = F;code = 70
char = N;code = 78
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 = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = d;code = 100
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
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char = t;code = 116
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char = i;code = 105
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char = o;code = 111
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char = e;code = 101
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char = o;code = 111
char = a;code = 97
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char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
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char = d;code = 100
char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = u;code = 117
char = m;code = 109
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char = (;code = 40
char = E;code = 69
char = R;code = 82
char = );code = 41
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = F;code = 70
char = N;code = 78
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 5;code = 53
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char = -;code = 45
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char = i;code = 105
char = s;code = 115
char = t;code = 116
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char = a;code = 97
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char = b;code = 98
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char = d;code = 100
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char = l;code = 108
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char = l;code = 108
char = i;code = 105
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char = K;code = 75
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char = ,;code = 44
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char = a;code = 97
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char = a;code = 97
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char = u;code = 117
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char = o;code = 111
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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 = l;code = 108
char = l;code = 108
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char = l;code = 108
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char = ;code = 32
char = T;code = 84
char = E;code = 69
char = R;code = 82
char = T;code = 84
char = -;code = 45
char = N;code = 78
char = H;code = 72
char = U;code = 85
char = C;code = 67
char = ,;code = 44
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char = a;code = 97
char = s;code = 115
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char = p;code = 112
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char = e;code = 101
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
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char = ;code = 32
char = f;code = 102
char = o;code = 111
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char = d;code = 100
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char = a;code = 97
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
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char = E;code = 69
char = R;code = 82
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
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char = s;code = 115
char = s;code = 115
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char = s;code = 115
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char = w;code = 119
char = a;code = 97
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char = d;code = 100
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char = d;code = 100
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char = i;code = 105
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char = K;code = 75
char = U;code = 85
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 = I;code = 73
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char = c;code = 99
char = o;code = 111
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
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char = ,;code = 44
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char = f;code = 102
char = o;code = 111
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char = l;code = 108
char = o;code = 111
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char = a;code = 97
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char = m;code = 109
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char = e;code = 101
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char = m;code = 109
char = a;code = 97
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char = ;code = 32
char = T;code = 84
char = E;code = 69
char = R;code = 82
char = T;code = 84
char = -;code = 45
char = N;code = 78
char = H;code = 72
char = U;code = 85
char = C;code = 67
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char = c;code = 99
char = e;code = 101
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char = I;code = 73
char = F;code = 70
char = N;code = 78
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char = #;code = 35
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char = 4;code = 52
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char = ;code = 32
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char = t;code = 116
char = r;code = 114
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char = s;code = 115
char = s;code = 115
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char = ,;code = 44
char = ;code = 32
char = n;code = 110
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char = t;code = 116
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char = s;code = 115
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char = A;code = 65
char = d;code = 100
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char = I;code = 73
char = F;code = 70
char = N;code = 78
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 5;code = 53
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char = a;code = 97
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char = h;code = 104
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char = o;code = 111
char = l;code = 108
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char = e;code = 101
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char = E;code = 69
char = R;code = 82
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = .;code = 46
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char = A;code = 65
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = 2;code = 50
char = 4;code = 52
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char = #;code = 35
char = 8;code = 56
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result sql = We have previously shown that adenoviral-mediated interferon α (Ad-IFNα) is cytotoxic both to cells that are sensitive to recombinant interferon α (IFNα) and to cells which are resistant to IFNα. The cancer cell-specific cytotoxic effects of Ad-IFNα involve three different mechanisms: 1. The direct effect of IFNα production causing cancer cell death in IFNα sensitive cells (1); 2. The direct effect of Ad-IFNα infection and high levels of IFNα expression in IFNα resistant cancer cells (2); and 3. The indirect effect of the Ad-IFNα bystander factors produced (2-4). After Ad-IFNα infection, the cells produce a large amount of perinuclear localized IFN protein. This protein over-load could be a major factor in the direct cancer cell death of those cells infected with Ad-IFNα compared with the indirect cytotoxic effects of the bystander factors produced. Here, we investigated whether a component of Ad-IFN-induced cell death involves protein overload-induced endoplasmic reticulum (ER) stress, using an IFNα-resistant human bladder cancer cell line (KU7), and the normal human urothelial cell line, TERT-NHUC, as preclinical models. We found that the two ER stress response pathways examined were activated in KU7 cells. In contrast, following treatment of the normal TERT-NHUC cells with Ad-IFNα, no ER stress signals were observed. In addition, no ER stress related changes were seen, when KU7 cells were exposed to conditioned medium from Ad-IFNα-treated KU7 cells, indicating that bystander produced cytotoxicity did not involve ER stress. After 24 h of Ad-IFNα infection, the KU7 cancer cells produced spliced X-box binding protein 1 and activating transcription factor 6 protein (ATF6), evoking an ER stress response that could contribute to Ad-IFNα induced apoptosis in these cancer cells. In addition, GADD153/CHOP, GADD34 and BAX were also subsequently modified following activation of the ER stress pathways, thereby signaling downstream effectors in a pro-apoptotic manner.

Publication: Cancer Gene Ther. 2011 Apr ;18(4)::260-4. :doi: 10.1038/cgt.2010.76.
Publication Date: 2011 Apr
Study Author(s): Zhang, X-Q;Yang, Z;Benedict, W F;
Institution: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Shortcut link to this study:
We have previously shown that adenoviral-mediated interferon α (Ad-IFNα) is cytotoxic both to cells that are sensitive to recombinant interferon α (IFNα) and to cells which are resistant to IFNα. The cancer cell-specific cytotoxic effects of Ad-IFNα involve three different mechanisms: 1. The direct effect of IFNα production causing cancer cell death in IFNα sensitive cells (1); 2. The direct effect of Ad-IFNα infection and high levels of IFNα expression in IFNα resistant cancer cells (2); and 3. The indirect effect of the Ad-IFNα bystander factors produced (2-4). After Ad-IFNα infection, the cells produce a large amount of perinuclear localized IFN protein. This protein over-load could be a major factor in the direct cancer cell death of those cells infected with Ad-IFNα compared with the indirect cytotoxic effects of the bystander factors produced. Here, we investigated whether a component of Ad-IFN-induced cell death involves protein overload-induced endoplasmic reticulum (ER) stress, using an IFNα-resistant human bladder cancer cell line (KU7), and the normal human urothelial cell line, TERT-NHUC, as preclinical models. We found that the two ER stress response pathways examined were activated in KU7 cells. In contrast, following treatment of the normal TERT-NHUC cells with Ad-IFNα, no ER stress signals were observed. In addition, no ER stress related changes were seen, when KU7 cells were exposed to conditioned medium from Ad-IFNα-treated KU7 cells, indicating that bystander produced cytotoxicity did not involve ER stress. After 24 h of Ad-IFNα infection, the KU7 cancer cells produced spliced X-box binding protein 1 and activating transcription factor 6 protein (ATF6), evoking an ER stress response that could contribute to Ad-IFNα induced apoptosis in these cancer cells. In addition, GADD153/CHOP, GADD34 and BAX were also subsequently modified following activation of the ER stress pathways, thereby signaling downstream effectors in a pro-apoptotic manner.
PMID: 21183949

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