Resistin stimulates PC-3 prostate cancer cell growth through stimulation of SOCS3 and SOCS5 genes.

Resistin and suppressors of cytokine signaling (SOCSs) have been reported to regulate prostate cancer (PCa) cell proliferation and survival, respectively. Whether any of the SOCS molecules mediate the mitogenic effect of resistin on PCa cells is unknown. Using PC-3 human PCa cells, we found that resistin upregulates the expression of and mRNA, but not mRNA, in a dose- and time-dependent manner. The resistin-induced increases in and expression and cell proliferation were prevented by pretreatment with specific inhibitors of the TLR4, ERK, p38 MAPK, JNK, PI3K, and JAK2 proteins. However, pretreatment with a TLR2 inhibitor had no effect on resistin-mediated and expression. In addition, the effects of resistin on , , and mRNA levels were cell type-specific. Overexpression of either or enhanced further resistin-stimulated growth of PC-3 cells, whereas silencing or antagonized resistin-increased cell growth. Further PCa tissue analysis demonstrated higher levels of , , , and mRNAs in cancer tissues than benign prostate hyperplasia and indicated positive correlations among , , and . These data suggest that SOCS5, TLR4, and, to a lesser extent, SOCS3 can mediate the mitogenic effect of resistin on PC-3 PCa cells.