Accession Number:

ADA580175

Title:

Nrdp1-Mediated ErbB3 Increase during Androgen Ablation and its Contribution to Androgen-Independence

Descriptive Note:

Final rept. 15 Aug 2012-28 Jan 2013

Corporate Author:

CALIFORNIA UNIV DAVIS

Personal Author(s):

Report Date:

2013-04-01

Pagination or Media Count:

177.0

Abstract:

Our data for the first time identifies Nrdp1 as an AR target that is androgen-regulated in castration resistant cells, but not in castration insensitive cells. Our new data shows that in cells where the AR is stabilized, and does not undergo degradation despite androgen withdrawal, it is able to transcribe PSA but not Nrdp1, whereas in cells where the AR is not stabilized, it can transcribe Nrdp1 and thereby regulate ErbB3 levels. Since we also showed earlier that ErbB3 signaling increase cell growth and suppress apoptosis, our results indicate that AR suppression of ErbB3 is a mechanism for keeping cells castration sensitive, whereas when this effect is lost, the cells become castration resistant. Further, we show that Filamin A nuclear localization keeps cells androgen responsive by destabilizing the AR, and maintaining its ability to transcriptionally regulate Nrdp1.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE