Suppressor of Cytokine Signaling (SOCS)-1 Is Expressed in Human Prostate Cancer and Exerts Growth-Inhibitory Function through Down-Regulation of Cyclins and Cyclin-Dependent Kinases

Abstract

Suppressor of cytokine signaling (SOCS) proteins play a pivotal role in the development and progression of various cancers. We have previously shown that SOCS-3 is expressed in prostate cancer, and its expression is inversely correlated with activation of signal transducer and activator of transcription factor 3. We hypothesized that SOCS-1, if expressed in prostate cancer cells, has a growth-regulatory role in this malignancy. The presence of both SOCS-1 mRNA and protein was detected in all tested cell lines. To assess SOCS-1 expression levels in vivo, we analyzed tissue microarrays and found a high percentage of positive cells in both prostate intraepithelial neoplasias and cancers. SOCS-1 expression levels decreased in samples taken from patients undergoing hormonal therapy but increased in specimens from patients who failed therapy. In LNCaP-interleukin-6- prostate cancer cells, SOCS-1 was up-regulated by interleukin-6 and in PC3-AR cells by androgens; such up-regulation was also found to significantly impair cell proliferation. To corroborate these findings, we used a specific small interfering RNA against SOCS-1 and blocked expression of the protein. Down-regulation of SOCS-1 expression caused a potent growth stimulation of PC3, DU-145, and LNCaP-interleukin-6- cells that was associated with the increased expression levels of cyclins D1 and E as well as cyclin-dependent kinases 2 and 4. In summary, we show that SOCS-1 is expressed in prostate cancer both in vitro and in vivo and acts as a negative growth regulator.

Immunohistochemical detection of tyrosine phosphatase SHP‐1 predicts outcome after radical prostatectomy for localized prostate cancer

“…57 The relationship of SHP-1 and SOCS-1/3 in IL-6 signaling is presently not known but they can be expected to be related to each other. In any case, our results suggest that, similar to SOCS-1, 56 the negative growth regulatory effect of SHP-1 (as in PC3 cells) is independent of STAT3. It is possible that various IL-6 responses such as those in proliferation and neuroendocrine differentiation are mediated by different signaling pathways and in a cell-specific manner.…”

PIM Kinase Inhibitors Downregulate STAT3Tyr705 Phosphorylation

“…Some of these results have been duplicated in prostate cancer cell lines, as downregulation of SOCS-1 by siRNA increases the proliferation of DU-145 cells. However, SOCS-3 may have an opposite function in DU-145 cells, as downregulation of SOCS-3 in DU-145 cells decreases cell proliferation (44,45). A role for PIM-3 in the regulation of SOCS proteins has not Tyr705 expression analysis are presented as in Fig.…”

Biochemical changes in some trace elements, antioxidant vitamins and their therapeutic importance in prostate cancer patients

“…1 Prostate cancer is the second most common cause of tumor related deaths in the western world. 2 Prostate cancer is the topmost killer among Nigerian men and constitutes 11% of all male cancers. 3 Prostate cancer is very heterogeneous in its etiology and progression but androgen signalling appears to be common key element in its development and cellular progression.…”