Accession Number:

ADA415597

Title:

Inhibitory Ah Receptor - Androgen Receptor Crosstalk in Prostate Cancer

Descriptive Note:

Annual rept. 15 Jan 2002-15 Jan 2003

Corporate Author:

TEXAS A AND M RESEARCH FOUNDATION COLLEGE STATION

Personal Author(s):

Report Date:

2003-02-01

Pagination or Media Count:

26.0

Abstract:

Treatment for prostate cancer depends on multiple factors including the stage of the tumor and expression of the androgen receptor AR Endocrine therapy can be used for treatment of early stage androgen-responsive tumors, whereas chemotherapy for later stage androgen- nonresponsive tumors is problematic We have investigated the aryl hydrocarbon receptor AhR as a potential target for treating prostate cancer using a new series of relatively non-toxic selective AhR modulators SAhRMs. Initial studies show that 22RVl, PC3 and LNCaP prostate cancer are Ah-responsive and 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD induces CYPlAl-dependent activities in all three cell lines Moreover, two SAhRMs namely diindolylmethane DIM and 6-methyl-1,3,8-trichlorodibenzofuran 6-MCDF inhibit growth of AR-positive 22RVl and AR-negative PC3 prostate cancer cells In addition, AhR ligands inhibit dihydrotestosterone-induced upregulation of AR protein in 22RVl cells suggesting a possible mechanism for inhibitory AhR-AR crosstalk The growth inhibitory effects of SAhRMs in PC3 cells suggests that AhR ligands also inhibit growth of androgen- nonresponsive cells.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE