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标题：Role of Coactivators and Corepressors in the Induction of the RARβ Gene in Human Colon Cancer Cells
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作者：Mi-Ock Lee ; Hyo-Jin Kang
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2002
卷号：25
期号：10
页码：1298-1302
DOI：10.1248/bpb.25.1298
出版社：The Pharmaceutical Society of Japan
摘要：We previously reported that the retinoic acid (RA) insensitivity of RARβ induction is a general feature of human colon cancer cells ( Biochem. Pharmacol. , 59: 485–496, 2000). In the present investigation, we analyzed potential transcriptional defects associated with the expression of the RARβ gene in colon cancer cells. Transfection of reporter constructs containing the RARβ gene promoter as well as truncated fragments of the promoter showed a significant induction of reporter activity by RA treatment in RA-sensitive HCT-15 cells, but not in RA-resistant DLD-1 cells. The results suggest that the transcriptional defect of RARβ expression may not be due to the presence of a specific cis -element in the RARβ promoter. Next we examined whether coactivators and corepressors of nuclear receptors were involved in the RA sensitivity of colon cancer cells. Transfection of coactivators such as CREB binding protein (CBP) and p300 up-regulated the RA-responsive element present in the RARβ promoter (βRARE) in DLD-1 cells up to the level in HCT-15, while coexpression of the nuclear receptor corepressor (NCoR) suppressed the βRARE activity in HCT-15 cells. The expression level of CBP protein was consistently higher in HCT-15, while that of NCoR and Sin3A was higher in DLD-1 cells. Treatment with the histone deacetylase inhibitor trichostatin A (TSA) increased both basal and RA-induced βRARE activity in DLD-1, indicating that histone deacetylase is involved in the regulation of RARβ gene expression. Taken together, our results show that differential function of coactivators and corepressors may determine the level of RARβ induction that may mediate retinoid action in colon cancer cells.
关键词：RARβ;retinoic acid;colon cancer;CBP/p300