A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy

The development and growth of prostate cancer depends on the androgen recep tor and its high-affinity binding of dihydrotestosterone, which derives fro m testosterone. Most prostate tumors regress after therapy to prevent testo sterone production by the testes, but the tumors eventually recur and cause death. A critical question is whether the androgen receptor mediates recur rent tumor growth after androgen deprivation therapy. Here we report that a majority of recurrent prostate cancers express high levels of the androgen receptor and two nuclear receptor coactivators, transcriptional intermedia ry factor 2 and steroid receptor coactivator 1, Overexpression of these coa ctivators increases androgen receptor transactivation at physiological conc entrations of adrenal androgen. Furthermore, we provide a molecular basis f or this activation and suggest a general mechanism for recurrent prostate c ancer growth.