@article{2971d9368a6649159925692880e1c54a,
title = "Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth",
abstract = "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.",
author = "Mulholland, {David J.} and Tran, {Linh M.} and Yunfeng Li and Houjian Cai and Ashkan Morim and Shunyou Wang and Seema Plaisier and Garraway, {Isla P.} and Jiaoti Huang and Graeber, {Thomas G.} and Hong Wu",
note = "Funding Information: We appreciate Drs. Guido Verhoeven and Karel De Gendt for generously supplying the AR conditional knockout line, UCLA Prostate SPORE for whole-mount human CaP and TMA sections, and Dr. Charles Sawyers for MDV3100 and communicating unpublished results. We thank Drs. Owen Witte, Robert Reiter, and Peter Nelson, and colleagues in our laboratories for their helpful comments and suggestions. D.J.M. was supported by NIH F32 CA112988-01 and CIRM TG2-01169, and L.M.T. is supported by NIH T32 CA009056. This work has been supported in part by an award from the Prostate Cancer Foundation (to H.W. and I.P.G.), Jean Perkins Foundation and Department of Defense (to I.P.G.) and a grant from NIH (R01 CA107166 and RO1 CA121110 to H.W.). ",
year = "2011",
month = jun,
day = "14",
doi = "10.1016/j.ccr.2011.05.006",
language = "English",
volume = "19",
pages = "792--804",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}