Tumor suppressive activity of prolyl isomerase Pin1 in renal cell carcinoma

Brian L Teng1, Kathryn E Hacker, Shufen Chen

  • 1Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

Molecular Oncology
|July 19, 2011
PubMed

Insights

Pin1 protein under-expression, potentially due to gene deletion, was observed in clear cell renal cell carcinoma (ccRCC). Restoring Pin1 suppressed ccRCC tumor growth, suggesting a mild tumor suppressive role.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Pin1 (Peptidyl-prolyl cis-trans isomerase) targets phosphorylated Ser/Thr-Pro bonds, influencing protein stability and function in tumor progression.
  • The role of Pin1 in cancer is complex, with its gene located on chromosome 19p13.2, a region prone to loss of heterozygosity.
  • Pin1 protein is notably under-expressed in kidney cancer, prompting investigation into its specific role in clear cell renal cell carcinoma (ccRCC).

Purpose of the Study:

  • To investigate the role of Pin1 in human clear cell renal cell carcinoma (ccRCC).
  • To determine the mechanisms underlying Pin1 reduction in ccRCC tumors.
  • To assess the impact of Pin1 restoration on ccRCC cell growth and tumor development.

Main Methods:

  • Analysis of PIN1 gene deletion and mRNA expression in ccRCC tumors.
  • Restoration of Pin1 expression in ccRCC cell lines deficient in Pin1.
  • Assessment of ccRCC cell growth in soft agar and a xenograft tumor model following Pin1 restoration.
  • Evaluation of the dependency of Pin1's tumor-suppressive effect on functional p53.

Main Results:

  • Evidence of PIN1 gene deletion and mRNA under-expression contributing to reduced Pin1 levels in ccRCC.
  • Restoration of Pin1 significantly attenuated ccRCC cell growth in vitro (soft agar) and in vivo (xenograft model).
  • The tumor-suppressive function of Pin1 in ccRCC appears to be dependent on the presence of functional p53.

Conclusions:

  • Pin1 reduction in ccRCC can occur via gene deletion and mRNA under-expression.
  • Restoring Pin1 expression inhibits ccRCC tumor growth, indicating a potential tumor suppressive role.
  • Pin1's tumor suppressive function in ccRCC may be linked to functional p53 status.

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