| First Author | Iseki M | Year | 2005 |
| Journal | Biochem Biophys Res Commun | Volume | 331 |
| Issue | 4 | Pages | 902-8 |
| PubMed ID | 15882963 | Mgi Jnum | J:98319 |
| Mgi Id | MGI:3577833 | Doi | 10.1016/j.bbrc.2005.04.014 |
| Citation | Iseki M, et al. (2005) Growth suppression of Leydig TM3 cells mediated by aryl hydrocarbon receptor. Biochem Biophys Res Commun 331(4):902-8 |
| abstractText | 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). |
