Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications

PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT.PKCζ expression was significantly higher in normal than in cancerous tissues (P < 0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P = 0.04), but no such association was found in TNM stage (P = 0.13). Tumors with higher PKCζ expression were associated with tumor size (P = 0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCζ siRNA and inhibitor.PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.The incidence of renal cell carcinoma (RCC) is increasing worldwide [1]. RCC mainly arises from renal tubular epithelia [2]. Surgical resection of the diseased tissue has been considered the only curative treatment [3]. Metastatic RCC (mRCC) is generally resistant to chemotherapy and hormonal therapy and marginally sensitive to immunotherapy [4]. Although several promising therapeutic strategies are now available for treating patients with mRCC, nearly all patients die of the metastatic disease. Research is ongoing to identify RCC-specific biomarkers that can improve early diagnosis, surveillance of tumor progression, and prediction of patient prognosis [5]. Markers such as growth factors, laminin, p53 mutations, and others, have been recently examined [6-8]. Unfortunately, none of these markers appear superior to the traditional staging and grading systems. RCC is al