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

Yeong-Shiau Pu1, Chao-Yuan Huang, Jyue-Yu Chen

  • 1Department of Urology, National Taiwan University College of Medicine, Taipei, Taiwan.

Abstract

Insights

Protein kinase C zeta (PKCζ) expression is reduced in renal cell carcinoma (RCC), correlating with increased tumor grade and size. Lower PKCζ levels indicate poor survival and chemoresistance in RCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Metastatic renal cell carcinoma (RCC) exhibits high resistance to chemotherapy, leading to poor patient outcomes.
  • Atypical protein kinase C zeta (PKCζ) is implicated in tumorigenesis, but its role in RCC clinical outcomes remains unclear.

Purpose of the Study:

  • To investigate the correlation between PKCζ expression levels and clinical outcomes in patients with renal cell carcinoma (RCC).
  • To assess the role of PKCζ in RCC tumorigenesis and chemoresistance.

Main Methods:

  • PKCζ mRNA and protein expression were quantified using real-time PCR and immunohistochemistry in 144 RCC tissue samples.
  • Cellular cytotoxicity and proliferation assays (MTT) were performed.
  • PKCζ was inhibited using siRNA and specific inhibitors in renal cancer cell lines.

Main Results:

  • PKCζ expression was significantly lower in cancerous tissues compared to normal tissues (P<0.0001).
  • Down-regulation of PKCζ correlated with elevated tumor grade (P=0.04) and tumor size (P=0.048).
  • Lower PKCζ expression was associated with poor survival in high-grade tumors and conferred chemoresistance to cisplatin and paclitaxel.

Conclusions:

  • PKCζ expression is significantly associated with tumorigenesis in renal cell carcinoma.
  • Down-regulation of PKCζ contributes to chemoresistance and poorer prognosis in RCC patients.

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