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

First Author  Mulholland DJ Year  2011
Journal  Cancer Cell Volume  19
Issue  6 Pages  792-804
PubMed ID  21620777 Mgi Jnum  J:172730
Mgi Id  MGI:5008676 Doi  10.1016/j.ccr.2011.05.006
Citation  Mulholland DJ, et al. (2011) Cell Autonomous Role of PTEN in Regulating Castration-Resistant Prostate Cancer Growth. Cancer Cell 19(6):792-804
abstractText  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.
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