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Altered expression of the clock gene machinery in kidney cancer patients

Gianluigi Mazzoccoli1, Ada Piepoli, Massimo Carella

  • 1Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. g.mazzoccoli@tin.it

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|March 23, 2012
PubMed
Abstract

Insights

Kidney cancer involves disrupted circadian clock genes, with specific genes like PER2, TIMELESS, and TIPIN showing altered expression. This deregulation may contribute to kidney cancer development and progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Chronobiology

Background:

  • Kidney cancer is linked to altered von Hippel-Lindau protein and hypoxia-inducible factor α pathways.
  • There are known interrelationships between hypoxia response and circadian pathways.
  • Circadian clock circuitry dysregulation is implicated in carcinogenesis.

Purpose of the Study:

  • To investigate the expression of clock genes within kidney cancer tissue.
  • To evaluate the circadian clock machinery's role in kidney cancer.

Main Methods:

  • Assessed mRNA expression of core clock genes (ARNTL1, ARNTL2, CLOCK, PER1, PER2, PER3, CRY1, CRY2, TIMELESS, TIPIN, CSNK1E) and a clock-controlled gene (SERPINE1).
  • Utilized DNA microarray assays and quantitative real-time PCR (qRT-PCR).
  • Analyzed matched primary tumor and non-tumorous kidney tissue from 11 patients.

Main Results:

  • Down-regulation of PER2, TIMELESS, and TIPIN observed in kidney tumors.
  • Up-regulation of SERPINE1 noted in kidney tumors.
  • Significant correlations found between PER2, TIMELESS, TIPIN, CSNK1E, and SERPINE1 mRNA levels.

Conclusions:

  • The circadian clock circuitry is deregulated in kidney cancer.
  • Altered expression of clock genes may play a role in kidney cancer onset and progression.

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