Growth suppression of Leydig TM3 cells mediated by aryl hydrocarbon receptor

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• 作者：Iseki ; Minoru ; Ikuta ; Togo ; Kobayashi ; Tetsuya ; Kawajiri ; Kaname
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：June 17, 2005
• 年：2005
• 卷：331
• 期：4
• 页码：902-908
• 全文大小：622 K

文摘

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces developmental toxicity in reproductive organs. To elucidate the function of AhR, we generated stable transformants of TM3 cells overexpressing wild-type aryl hydrocarbon receptor (AhR) or its mutants which carried mutations in nuclear localization signal or nuclear export signal. In the presence of 3-methylcholanthrene (MC), proliferation of the cells transfected with wild-type AhR was completely suppressed, whereas cells expressing AhR mutants proliferated in a manner equivalent to control TM3 cells, suggesting AhR-dependent growth inhibition. The suppression was associated with up-regulation of cyclin-dependent kinase inhibitor p21^Cip1, which was abolished by pretreatment with actinomycin D. A p38 MAPK specific inhibitor, SB203580, blocked the increase of p21^Cip1 mRNA in response to MC. Treatment with indigo, another AhR ligand, failed to increase of p21^Cip1 mRNA, although up-regulation of mRNA for CYP1A1 was observed. These data suggest AhR in Leydig cells mediates growth inhibition by inducing p21^Cip1.