Accession Number : ADA436964


Title :   Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer


Descriptive Note : Annual rept. 15 Jan 2004-15 Jan 2005


Corporate Author : TEXAS A AND M RESEARCH FOUNDATION COLLEGE STATION


Personal Author(s) : Safe, Stephan H


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a436964.pdf


Report Date : Feb 2005


Pagination or Media Count : 25


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 CYP1A1-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. In addition, substituted DIMs inhibit growth of prostate cancer cells and modulate AR expression, and these are currently being investigated.


Descriptors :   *CROSSTALK , *RECEPTOR SITES(PHYSIOLOGY) , *ANDROGENS , *PROSTATE CANCER , PROTEINS , NEOPLASMS , HYDROCARBONS , LIGANDS , THERAPY , GROWTH(PHYSIOLOGY) , ENDOCRINE GLANDS , CHEMOTHERAPY , SENSE ORGANS , ARYL RADICALS , INHIBITION , CELLS(BIOLOGY) , MODULATORS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE