Androgen receptor remains critical for cell-cycle progression in androgen-independent CWR22 prostate cancer cells. Yuan X, Li T, Wang H, Zhang T, Barua M, Borgesi RA, Bubley GJ, Lu ML, Balk SP, Hematology/Oncology Division, Beth Israel Deaconess Medical Center, Boston, MA

Research output: Contribution to journalShort surveypeer-review

Abstract

The majority of prostate cancers (PCa) that relapse after androgen deprivation therapy (androgen-independent PCa) continue to express androgen receptor (AR). To study the functional importance of AR in these tumors, we derived androgen-independent CWR22 PCa xenografts in castrated mice and generated a cell line from one of these xenografts (CWR22R3). Similarly to androgen-independent PCa in patients, the relapsed xenografts and cell line expressed AR and were resistant to treatment with bicalutamide. However, expression of the AR-regulated PSA gene in the CWR22R3 cell line was markedly decreased compared to the relapsed xenografts in vivo. Transfections with androgen-regulated reporter genes further indicated that the cells lacked androgen-independent AR transcriptional activity and were not hypersensitive to low androgen concentrations despite constitutive activation of the Erk/MAP kinases. Nonetheless, AR remained essential for androgen-independent growth because retroviral shRNA-mediated AR down-regulation resulted in marked long-term growth suppression. This was associated with increased levels of p27(kip1) and hypophosphorylation of retinoblastoma protein but not with decreases in D-type cyclin levels or MAP kinase activation. These results reveal a potentially critical function of AR in androgen-independent PCa that is distinct from its previously described transcriptional or nontranscriptional functions.

Original languageEnglish (US)
Pages (from-to)178-179
Number of pages2
JournalUrologic Oncology: Seminars and Original Investigations
Volume25
Issue number2
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Urology

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