Accession Number:

ADA390074

Title:

Characterization of Factors Affecting Androgen Receptor Transcriptional Regulation in Prostate Cancer

Descriptive Note:

Annual rept. 1 Jan 2000-31 Dec 2000

Corporate Author:

NEW YORK UNIV NY SCHOOL OF MEDICINE

Personal Author(s):

Report Date:

2001-01-01

Pagination or Media Count:

13.0

Abstract:

The androgen receptor AR is a ligand-regulated transcription factor that stimulates both normal and malignant prostate cell growth. To understand the mechanism of AR function, we sought to identify novel factors that interact with AR N-terminus by use of a yeast two-hybrid system. A 157-amino acid protein termed ART-27 was cloned and shown to interact with an AR N-terminal subdomain residues 153-336, localize predominantly to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 overexpression also enhanced the transcriptional activation by ARsub 153-336 fused to LexA DNA binding domain, but not other AR N-terminal subdomains, lending support to the notion that ART-27 mediates its effect via an interaction with a defined region of the AR N-terminus. ART-27 overexpression also lowers the concentration of androgen required for AR-dependent transcriptional activation. ART-27 gene maps to a region of the X-chromosome near the AR locus, which is amplified in a subset of prostate cancers, suggesting that overexpression of ART-27 may facilitate malignant cell growth by increasing the sensitivity and activity of AR to androgen in target cells.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE