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VHL Dependent Expression of REDD1 and PDK3 Proteins in Clear-cell Renal Cell Carcinoma

Bojana B Ilic1, Jadranka A Antic1, Jovana Z Bankovic1

  • 1Clinic for Endocrinology, Diabetes and Metabolic Diseases, Medical School, University of Belgrade, Department of Neuroendocrine Tumors and Hereditary Cancer Syndromes, Belgrade, Serbia.

Journal of Medical Biochemistry
|December 25, 2018
PubMed
Abstract

Insights

VHL gene mutations impact REDD1 and PDK3 protein expression in clear-cell renal cell carcinoma (ccRCC). mTOR, eIF4E-BP1, and AMPK levels remain unaffected by VHL status.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Sporadic clear-cell renal cell carcinoma (ccRCC) is linked to VHL gene mutations, increased mTOR activity, and altered metabolism.
  • Understanding the VHL gene's role in ccRCC protein expression is crucial for targeted therapies.

Purpose of the Study:

  • To investigate the effect of VHL (von Hippel-Lindau) gene mutational status on the expression of key proteins: mTOR, eIF4E-BP1, AMPK, REDD1, and PDK3.
  • To elucidate the relationship between VHL inactivation and specific protein expression patterns in ccRCC.

Main Methods:

  • Protein expression analysis using Western blot on tumor samples from ccRCC patients.
  • Categorization of samples based on VHL gene status: biallelic inactivation, monoallelic inactivation, and wild-type (wtVHL).

Main Results:

  • mTOR, eIF4E-BP1, and AMPK expression were independent of VHL mutational status.
  • REDD1 was underexpressed in tumors with monoallelic VHL inactivation and overexpressed in tumors with biallelic VHL inactivation compared to controls.
  • PDK3 was overexpressed in wild-type VHL tumors, with its expression significantly correlated with AMPK levels in wtVHL ccRCC.

Conclusions:

  • VHL gene status influences REDD1 and PDK3 protein expression in sporadic ccRCC.
  • mTOR, eIF4E-BP1, and AMPK expression are not directly regulated by VHL mutational status in ccRCC.
  • This study highlights VHL-dependent regulation of PDK3 and REDD1, offering insights into ccRCC pathogenesis.
Keywords:
VHL geneclear-cell renal cell carcinomamammalian target of rapamycinpyruvate dehydrogenase kinase 3regulated in development and DNA damage responses

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