Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells

Interleukin 6 (IL-6) plays important roles in the immune system, hematopoie sis, as well as the growth of various tumors. Androgens are important in th e initiation and progression of prostate cancer and their effects are media ted by androgen receptor (AR). Here we present a molecular mechanism for th e effects of IL-6 on prostate cancer cells through a cross-talk between IL- 6 and AR signaling pathways. IL-6-induced activation of signal transducer a nd activator of transcription 3 (STAT3) was augmented by AR in the presence of dihydrotestosterone (DHT). In addition, DHT treatment augmented endogen ous STAT3-mediated gene expression by IL-6. Conversely, DHT-induced AR acti vity was increased by IL-6, and a dominant negative form of STAT3 inhibited AR activation. In contrast, DHT-mediated enhancement of STAT3 activation w as inhibited by flutamide, an AR antagonist. We provide evidence that these activities are due to direct physical interactions between STAT3 and AR in prostate cancer cells. (C) 2001 Academic Press.