- 作者: Yeong-Shiau Pu Pu, Chao-Yuan Huang, Jyue-Yu Chen, Wang-Yi Kang, Ying-Chu Lin, Yu-Shiang Shiu, Shu-Ju Chuang, Hong-Jeng Yu, Ming-Kuen Lai, Yu-Chieh Tsai, Wen-Jeng Wu and Tzyh-Chyuan Hour
- 作者服務機構: Departments of Urology, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCzeta is an important regulator of tumorigenesis. However, the correlation between PKCzeta expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCzeta expression in human RCC.
Methods: PKCzeta 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.
Results: PKCzeta expression was significantly higher in normal than in cancerous tissues (P < 0.0001) by real-time PCR and IHC. Similarly, PKCzeta expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCzeta 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 PKCzeta expression were associated with tumor size (P = 0.048). Expression of higher PKCzeta found a poor survival in patients with high tumor grade. Down-regulation of PKCzeta showed the significant chemoresistance in RCC cell lines. Inactivation of PKCzeta expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCzeta siRNA and inhibitor. Conclusions: PKCzeta expression was associated with tumorigenesis and chemoresistance in RCC. - 中文關鍵字: --
- 英文關鍵字: Renal cell carcinoma, PKCδ, Immunohistochemistry, Chemoresistance, Cytotoxicity