Nuclear factor-κB signaling pathway is involved in phospholipase Cε-regulated proliferation in human renal cell carcinoma cells

Phospholipase C epsilon (PLC epsilon), a downstream effector of small GTPase superfamily, has been identified to play a crucial role in tumorigenesis. Previously, our studies have showed that PLC epsilon promotes proliferation of renal cell carcinoma (RCC) cells. However, the molecular mechanisms by which PLC epsilon enhances the survival phenotype of RCC cells are still not fully instructed. In the present study, we first demonstrated that PLC epsilon was highly expressed and had a close correlation with Ki67 protein expression in RCC tissue samples. Further, we found that downregulation of PLC epsilon expression repressed growth and induced apoptosis in RCC cells. In addition, we reported a mechanism by which knockdown of PLC epsilon gene potently suppressed the nuclear factor kappa (NF-kappa B) signaling pathway through action on inhibitor of kappa B kinase. Moreover, silencing PLC epsilon gene decreased vascular endothelial growth factor (VEGF) expression, which was a downstream growth factor of NF-kappa B signaling pathway. Finally, downregulation of VEGF was severely enhanced by treatment cells with NF-kappa B specific inhibitor BAY11-7028 in PLC epsilon knockdown cells. Taken together, these findings suggest that PLC epsilon promotes RCC cell growth via NF-kappa B-mediated upregulation of VEGF.