Protein inhibitor of activated STAT3 regulates androgen receptor signalingin prostate carcinoma cells

Protein inhibitor of activated STAT3 (PIAS3) is a specific inhibitor of sig nal transducer and activator of transcription 3 (STAT3). PIAS3 binds to STA T3 and inhibits its DNA-binding activity, and thereby STAT3-mediated gene a ctivation. PIAS1, another member of the PIAS family, was recently shown to interact with the androgen receptor (AR), a nuclear hormone receptor that h as an important role in both physiological and pathological processes, and acts as a cofactor for AR. Here we demonstrate that PIAS3 is expressed in p rostate cancer cells and its expression is induced in response to dihydrote stosterone (DHT) treatment. Ectopic overexpression of PIAS3 suppressed AR-m ediated gene activation induced by DHT-stimulation in LNCaP cells. We provi de evidence that these activities were due to direct physical interactions between PIAS3 and AR. These results indicate that PIAS3 acts as a coregulat or of AR signaling pathway in prostate cancer cells, (C) 2000 Academic Pres s.