Growth suppression of Leydig TM3 cells mediated by aryl hydrocarbon receptor

Journal Article · Fri Jun 17 04:00:00 EDT 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.04.014· OSTI ID:20710789

Iseki, Minoru ^[1]; Ikuta, Togo ^[1]; Kobayashi, Tetsuya ^[2]; Kawajiri, Kaname ^[1]

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1. Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama (Japan)
2. Department of Regulation Biology, Faculty of Science, Saitama University, Saitama (Japan)

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{sup Cip1}, which was abolished by pretreatment with actinomycin D. A p38 MAPK specific inhibitor, SB203580, blocked the increase of p21{sup Cip1} mRNA in response to MC. Treatment with indigo, another AhR ligand, failed to increase of p21{sup Cip1} mRNA, although up-regulation of mRNA for CYP1A1 was observed. These data suggest AhR in Leydig cells mediates growth inhibition by inducing p21{sup Cip1}.

• OSTI ID: 20710789
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 331; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
60 APPLIED LIFE SCIENCES
ACTINOMYCIN
CELL PROLIFERATION
DIOXIN
INDIGO
INHIBITION
LIGANDS
MUTANTS
MUTATIONS
ORGANS
RECEPTORS
TOXICITY