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

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.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2013
Accession Number
ADA580175

Entities

People

  • Paramita M Ghosh

Organizations

  • University of California

Tags

DTIC Thesaurus Topics

  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Genetics
  • Health Services
  • Oncology
  • Organic Chemistry
  • Peptide Growth Factors
  • Proteins
  • Proteomics

Fields of Study

  • Biology

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