Characterization of Factors Affecting Androgen Receptor Transcriptional Regulation in Prostate Cancer
Annual rept. 1 Jan 2000-31 Dec 2000
NEW YORK UNIV NY SCHOOL OF MEDICINE
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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.
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