AbstractBACKGROUNDSignal transducer and activator of transcription (STAT)‐6 is a member of the STAT family of latent transcription factors. In this investigation, we examined STAT6 expression in clinical prostate cancer tissue specimen and determined its role in prostate cell proliferation and migration.METHODSSTAT6 expression in cell lines and tissues was analyzed by RT‐PCR, IHC and/or immunoblot analyses. Down‐regulation of STAT6 expression was achieved by STAT6 siRNA and its effect on cell migration and apoptosis was measured.RESULTSSTAT6 is highly expressed in the fibromuscular stroma of prostate cancer specimens. STAT6 is also expressed in the malignant epithelial layer and prostate intraepithelial neoplasia (PIN). STAT6 expression was significantly correlated with high histological grades of prostate cancer as well as with tumor size. Our data indicate deregulated STAT6 mRNA and protein expression in prostate cancer cells with high levels in the non‐cancerous HPV 18C‐1 and cancerous DU145 cell lines and low levels in PC3 and LNCaP cells. Phosphorylated STAT6 was expressed in all three cancer cell lines DU145, PC3, and LNCaP. Down‐regulation of STAT6 using siRNA leads to the induction of early apoptosis in DU145 cells and inhibits migration of these cells. Significant reduction in cell viability and transcriptional down‐regulation of the anti‐apoptotic protein Bcl‐XL was observed followed by STAT6 down‐regulation in DU145 cells. Interestingly STAT6 also regulates transcription of 15‐lipoxygenase‐1 gene in DU145 cells.CONCLUSIONSOur data suggest that STAT6 is a survival factor in prostate cancer and regulates the genetic transcriptional program that is responsible for prostate cancer progression. Prostate 67: 1550–1564, 2007. © 2007 Wiley‐Liss, Inc.