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RARgamma acts as a tumor suppressor in mouse keratinocytes

Chang Feng Chen1, Philippe Goyette, David Lohnes

  • 1Division of Experimental Medicine, McGill University, Quebec, Canada.

Oncogene
|April 20, 2004
PubMed

Insights

All-trans retinoic acid (RA) receptors, particularly RARgamma, act as tumor suppressors. Loss of RARgamma in keratinocytes promotes squamous cell carcinoma, while its presence inhibits tumor development.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Oncology

Background:

  • All-trans retinoic acid (RA), the active form of vitamin A, is crucial for development and adult homeostasis.
  • Evidence suggests RA, via retinoic acid receptors (RARs), can inhibit tumor growth.

Purpose of the Study:

  • To investigate the direct role of RARs in epidermal tumorigenesis.
  • To assess the specific functions of RARalpha and RARgamma in keratinocytes during tumor development.

Main Methods:

  • Utilized keratinocytes genetically modified to lack specific RAR types (RARalpha or RARgamma).
  • Induced squamous cell carcinoma using v-Ha-Ras.
  • Assessed RA-induced effects on cell cycle arrest and apoptosis.
  • Reconstituted RAR expression in null cells to confirm receptor function.

Main Results:

  • Loss of RARgamma, but not RARalpha, predisposed keratinocytes to v-Ha-Ras-induced squamous cell carcinoma.
  • Ablation of RARgamma, but not RARalpha, abolished RA-induced cell cycle arrest and apoptosis.
  • Restoring RAR expression in null cells reversed the tumorigenic potential and restored RA sensitivity.

Conclusions:

  • Endogenous RARgamma plays a significant role as a tumor suppressor in murine keratinocytes.
  • RARgamma mediates RA's effects on cell cycle arrest and apoptosis, crucial for preventing epidermal tumors.

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