Inhibitory Ah Receptor - Androgen Receptor Crosstalk in Prostate Cancer
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 22RV1, 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-l,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 22RV1 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA423669
Entities
People
- Stephen H. Safe
Organizations
- Texas A&M University