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pVHL and PTEN tumour suppressor proteins cooperatively suppress kidney cyst formation

Ian J Frew1, Claudio R Thoma, Strahil Georgiev

  • 1Institute of Cell Biology, ETH Zurich, Zurich, Switzerland.

The EMBO Journal
|May 24, 2008
PubMed

Insights

Von Hippel-Lindau (VHL) disease causes kidney cysts and clear cell renal cell carcinoma (ccRCC). Combined inactivation of VHL and PTEN genes in mice causes rapid cyst formation, suggesting PTEN cooperates with VHL to prevent kidney cysts.

Area of Science:

  • Oncology
  • Genetics
  • Cell Biology

Background:

  • Von Hippel-Lindau (VHL) disease is linked to renal cysts and clear cell renal cell carcinoma (ccRCC) due to biallelic VHL gene inactivation.
  • The development of renal cysts and ccRCC in VHL disease is thought to involve additional genetic alterations.
  • Activation of the phosphatidylinositol-3-kinase (PI3K) pathway is observed in VHL disease kidney lesions.

Purpose of the Study:

  • To investigate the role of PTEN in VHL disease-associated kidney cyst formation.
  • To explore the cooperation between VHL and PTEN tumor suppressor genes in kidney epithelial cells.
  • To understand the contribution of primary cilia defects in VHL disease pathogenesis.

Main Methods:

  • Conditional inactivation of Vhlh and Pten tumor suppressor genes in mouse kidneys.
  • Histological analysis of kidney tissues to identify cyst formation and cellular changes.
  • Assessment of primary cilia presence and integrity in kidney epithelial cells.

Main Results:

  • Combined inactivation of Vhlh and Pten in mouse kidneys led to rapid cyst formation.
  • Inactivation of either Vhlh or Pten alone did not result in significant cyst formation.
  • Cells lining the cysts often lacked primary cilia, indicating a potential role in disease progression.

Conclusions:

  • PTEN tumor suppressor protein cooperates with pVHL to suppress kidney cyst development.
  • Loss of PTEN function exacerbates cystogenesis in the context of VHL deficiency.
  • Defects in primary cilia may contribute to the pathogenesis of VHL disease-related kidney lesions.

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