title: Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications.
abstract: 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 PKCζ is an important regulator of tumorigenesis. However, the correlation between PKCζ expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.
authors.affiliation: Department of Urology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.forename: Jyue-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Wang-Yi
authors.initials: WY
authors.lastname: Kang
authors.forename: Ying-Chu
authors.initials: YC
authors.lastname: Lin
authors.forename: Yu-Shiang
authors.initials: YS
authors.lastname: Shiu
authors.forename: Shu-Ju
authors.initials: SJ
authors.lastname: Chuang
authors.forename: Hong-Jeng
authors.initials: HJ
authors.lastname: Yu
authors.forename: Ming-Kuen
authors.initials: MK
authors.lastname: Lai
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Tsai
authors.forename: Wen-Jeng
authors.initials: WJ
authors.lastname: Wu
authors.forename: Tzyh-Chyuan
authors.initials: TC
authors.lastname: Hour
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000627:therapeutic use; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D005562:Formazans / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000627:therapeutic use; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000737:chemistry; D000099221:Protein Kinase C zeta
chemical_list: D002945:Cisplatin; D005562:Formazans; D017239:Paclitaxel; D011493:Protein Kinase C; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D000099221:Protein Kinase C zeta; C079782:MTT formazan