Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and testosterone signal transduction pathways in LNCaP prostate cancer cells

N. R. Jana, S. Sarkar, M. Ishizuka, J. Yonemoto, C. Tohyama, H. Sone

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds modulate various endocrine functions by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. In the present study, we investigated the effects of TCDD on testosterone signal transduction pathways and vice versa in the androgen receptor (AR) positive LNCaP prostate cancer cell line. TCDD induced CYP1A1 mRNA and related enzyme activity in these cells, with dose and time-dependence. Both normal and testosterone-stimulated cell growth was inhibited by TCDD. The expression levels of the aryl hydrocarbon receptor (AhR), the aryl hydrocarbon receptor nuclear translocater (ARNT), and AR were not affected by exposure to TCDD at a dose of 10 nM for a 24 hr time period. Testosterone treatment dose-dependently inhibited the TCDD-induced CYP1A1 mRNA accumulation and related enzyme activity. Reciprocally, TCDD also dose-dependently inhibited testosterone-dependent transcriptional activity and testosterone-regulated prostate specific antigen (PSA) expression. Taken together, these results demonstrate antiandrogenic functions of TCDD and a specific ligand-induced bilateral transcriptional interference between TCDD and testosterone mediated signal transduction pathways.

Original languageEnglish (US)
Pages (from-to)462-468
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume256
Issue number3
DOIs
StatePublished - Mar 24 1999

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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