Overexpression of signal transducer and activator of transcription (STAT-3 and STAT-5) transcription factors and alteration of suppressor of cytokine signaling (SOCS-1) protein in prostate cancer

Background: Prostate cancer is a leading cause of mortality in men worldwide especially in developing countries like India. The molecular mechanisms of the oncogenic signaling pathway(s) that are involved in prostate carcinogenesis play a crucial role in disease progression and persistence. There is an important role of signal transducer and activator of transcriptions (STATs) particularly STAT-3 and STAT-5 and its negative regulator suppressor of cytokine signaling-1 (SOCS-1). Methods: In the present study, the expression and localization of STAT and SOCS-1 proteins in prostate cancer by immunohistochemistry in a total of 150 formalin-fixed, paraffin-embedded human prostate tissues of different grade obtained by radical prostatectomies or transurethral resection. Results: A significantly strong STAT-3 expression pattern in 68% (65/95) prostate cancer cases as compared to 12% (5/55) in benign prostatic hyperplasia (BPH) controls (P < 0.001) was observed. Interestingly the SOCS-1 expression was found to be significantly elevated in prostate cancer cases (P < 0.001). Conclusions: The present study demonstrates overexpression of STAT-3 and STAT-5 proteins and a contrasting role of SOCS-1 in prostate cancer. These results suggest a critical association between altered expression of STAT-3 and STAT-5 with SOCS-1 and indicate its potential role as a negative regulator independent of JAK-STAT pathway in tumorigenic transformation of prostate tissue. The results of the present report focuses on the fundamental differences in major oncogenic signaling cascades between benign and malignant form of prostate tissue that plays a crucial role in prostate cancer biology.