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RARγ acts as a tumor suppressor in mouse keratinocytes

Oncogene volume 23, pages 5350–5359 (2004)Cite this article

Abstract

All-trans retinoic acid (RA), the principle biologically active form of vitamin A, is essential for many developmental process as well as homeostasis in the adult. Many lines of evidence also suggest that RA, acting through the RA receptors (RARs), can also suppress growth of tumors of diverse origin. To assess directly the role of the RARs in a model of epidermal tumorigenesis, we investigated the incidence of tumor formation using keratinocytes lacking specific RAR types. Our data suggest that loss of RARγ, but not RARα, predisposed keratinocytes to v-Ha-Ras-induced squamous cell carcinoma. We also found that ablation of RARγ, but not RARα, abolished RA-induced cell cycle arrest and apoptosis in these keratinocytes. Reconstitution of receptor expression into RAR-null cells restored sensitivity to RA, and reversed the tumorigenic potential of receptor-deficient keratinocytes. These data strongly support a tumor suppressor effect for the RARs, in particular endogenous RARγ, in murine keratinocytes.

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Abbreviations

AP-1:

activating protein 1

DMSO:

dimethyl sulfoxide

ERK:

extracellular signal-regulated kinase

JNK:

c-Jun amino-terminal kinase

RA:

all-trans retinoic acid

RAR:

retinoic acid receptor

RARE:

retinoic acid-responsive element

RXR:

retinoid X receptor

SCC:

squamous cell carcinoma

s.c.:

subcutaneous

TPA:

12-O-tetradecanolphorbol-13-acetate

TRE:

TPA-responsive element

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Acknowledgements

We would like to thank H Liénard and C Charbonneau for assistance with photography, SH Yuspa for the v-Ha-ras retrovirus, and members of the laboratory for suggestions. This work was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society. CFC was supported by a scholarship from the Cancer Research Society, Inc., and PG by a fellowship from the Canadian Institutes for Health Research. DL is a chercheur bourcier (Senior) of the Fonds de la Recherches en Santé de Québec.

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  1. Philippe Goyette

    Present address: BioLactis, Laval, Quebec, Canada

Authors and Affiliations

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

    Chang Feng Chen & David Lohnes

  2. Clinical Research Institute of Montreal, Quebec, Canada

    Chang Feng Chen, Philippe Goyette & David Lohnes

  3. Department of Molecular Biology, University of Montreal, Quebec, Canada

    David Lohnes

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Correspondence to David Lohnes.

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Chen, C., Goyette, P. & Lohnes, D. RARγ acts as a tumor suppressor in mouse keratinocytes. Oncogene 23, 5350–5359 (2004). https://doi.org/10.1038/sj.onc.1207682

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