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char = g;code = 103
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char = .;code = 46
result sql = Cancer prevention by retinoids and carotenoids: independent action on a common target.
Cancer prevention by retinoids and carotenoids: independent action on a common target.
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char = d;code = 100
char = u;code = 117
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char = i;code = 105
char = c;code = 99
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char = l;code = 108
char = a;code = 97
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char = a;code = 97
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char = 3;code = 51
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char = (;code = 40
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
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char = e;code = 101
char = d;code = 100
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = 1;code = 49
char = 0;code = 48
char = T;code = 84
char = 1;code = 49
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char = .;code = 46
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char = m;code = 109
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char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
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char = s;code = 115
char = i;code = 105
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result sql = Virtually all human tumors are deficient in gap junctional communication (GJC) and the restoration of GJC by forced expression of connexins reduces indices of neoplasia. The expression of connexin 43 (Cx43) is upregulated by cancer-preventive retinoids and carotenoids which correlates with the suppression of carcinogen-induced transformation in 10T1/2 cells. However, the molecular mechanism for upregulated expression is poorly understood. The retinoic acid receptor antagonist, Ro 41-5253, suppressed retinoid-induced Cx43 protein expression in 10T1/2 cells and the induction of a Cx43 luciferase reporter construct in F9 cells, but did not suppress protein expression or reporter activity induced by the non-pro-vitamin A carotenoid astaxanthin. In contrast, Cx43 induction by astaxanthin, but not by a RAR-specific retinoid, was inhibited by GW9662, a PPAR-gamma antagonist. Neither compound required protein synthesis for the induction of Cx43 mRNA, nor was the 5.0 h half-life of Cx43 mRNA altered, indicating direct transcriptional activation. The responsive region was found within -158 bp and +209 bp of the transcription start site. Site directed mutagenesis of a GC-box in this region increased basal levels of transcription and loss of retinoid responsiveness. Simultaneous treatment with a retinoid and beta-carotene or astaxanthin resulted in supra-additive Cx43 expression, again indicating separate mechanisms of gene regulation.

Publication: Biochim. Biophys. Acta 2005 May 30 ;1740(2)::170-8.
Publication Date: 2005 May 30
Study Author(s): Bertram, John S;Vine, Alex L;
Institution: Cancer Research Center of Hawaii, University of Hawaii at Manoa, 1236 Lauhala St., Honolulu, Hawaii, USA. [email protected]
Shortcut link to this study:
Virtually all human tumors are deficient in gap junctional communication (GJC) and the restoration of GJC by forced expression of connexins reduces indices of neoplasia. The expression of connexin 43 (Cx43) is upregulated by cancer-preventive retinoids and carotenoids which correlates with the suppression of carcinogen-induced transformation in 10T1/2 cells. However, the molecular mechanism for upregulated expression is poorly understood. The retinoic acid receptor antagonist, Ro 41-5253, suppressed retinoid-induced Cx43 protein expression in 10T1/2 cells and the induction of a Cx43 luciferase reporter construct in F9 cells, but did not suppress protein expression or reporter activity induced by the non-pro-vitamin A carotenoid astaxanthin. In contrast, Cx43 induction by astaxanthin, but not by a RAR-specific retinoid, was inhibited by GW9662, a PPAR-gamma antagonist. Neither compound required protein synthesis for the induction of Cx43 mRNA, nor was the 5.0 h half-life of Cx43 mRNA altered, indicating direct transcriptional activation. The responsive region was found within -158 bp and +209 bp of the transcription start site. Site directed mutagenesis of a GC-box in this region increased basal levels of transcription and loss of retinoid responsiveness. Simultaneous treatment with a retinoid and beta-carotene or astaxanthin resulted in supra-additive Cx43 expression, again indicating separate mechanisms of gene regulation.
PMID: 15949684

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