当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and testosterone signal transduction pathways in LNCaP prostate cancer cells.

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

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 translocator (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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Jana NR,Sarkar S,Ishizuka M,Yonemoto J,Tohyama C,Sone H

doi

10.1006/bbrc.1999.0367

subject

Has Abstract

pub_date

1999-03-24 00:00:00

pages

462-8

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(99)90367-4

journal_volume

256

pub_type

杂志文章

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