Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth.

Journal Article (Journal Article)

Alteration of the PTEN/PI3K pathway is associated with late-stage and castrate-resistant prostate cancer (CRPC). However, how PTEN loss is involved in CRPC development is not clear. Here, we show that castration-resistant growth is an intrinsic property of Pten null prostate cancer (CaP) cells, independent of cancer development stage. PTEN loss suppresses androgen-responsive gene expressions by modulating androgen receptor (AR) transcription factor activity. Conditional deletion of Ar in the epithelium promotes the proliferation of Pten null cancer cells, at least in part, by downregulating the androgen-responsive gene Fkbp5 and preventing PHLPP-mediated AKT inhibition. Our findings identify PI3K and AR pathway crosstalk as a mechanism of CRPC development, with potentially important implications for CaP etiology and therapy.

Full Text

Duke Authors

Cited Authors

  • Mulholland, DJ; Tran, LM; Li, Y; Cai, H; Morim, A; Wang, S; Plaisier, S; Garraway, IP; Huang, J; Graeber, TG; Wu, H

Published Date

  • June 14, 2011

Published In

Volume / Issue

  • 19 / 6

Start / End Page

  • 792 - 804

PubMed ID

  • 21620777

Pubmed Central ID

  • PMC3157296

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2011.05.006


  • eng

Conference Location

  • United States