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Originally published In Press as doi:10.1074/jbc.M909382199 on March 19, 2000

J. Biol. Chem., Vol. 275, Issue 22, 16497-16505, June 2, 2000
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Characterization of Retinoic Acid Receptor-deficient Keratinocytes*

Philippe GoyetteDagger , Chang Feng ChenDagger §, Wei WangDagger , Francois SeguinDagger , and David LohnesDagger §||

From the Departments of  Molecular Biology, Université de Montréal, § Division of Experimental Medicine, McGill University, and the Dagger  Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins, Ouest, Montréal, Québec H2W 1R7, Canada

Retinoids are essential for normal epidermal growth and differentiation and show potential for the prevention or treatment of various epithelial neoplasms. The retinoic acid receptors (RARalpha , -beta , and -gamma ) are transducers of the retinoid signal. The epidermis expresses RARgamma and RARalpha , both of which are potential mediators of the effects of retinoids in the epidermis. To further investigate the role(s) of these receptors, we derived transformed keratinocyte lines from wild-type, RARalpha , RARgamma , and RARalpha gamma null mice and investigated their response to retinoids, including growth inhibition, markers of growth and differentiation, and AP-1 activity. Our results indicate that RARgamma is the principle receptor contributing to all-trans-retinoic acid (RA)-mediated growth arrest in this system. This effect partially correlated with inhibition of AP-1 activity. In the absence of RARs, the synthetic retinoid N-(4-hydroxyphenyl)-retinamide inhibited growth; this was not observed with RA, 9-cis RA, or the synthetic retinoid (E)-4-[2-(5, 5, 8, 8 tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propenyl] benzoic acid. Finally, both RARalpha and RARgamma differently affected the expression of some genes, suggesting both specific and overlapping roles for the RARs in keratinocytes.


* This work was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society (to D. L.) and by personnel support from the Medical Research Council of Canada (to P. G.), the Cancer Research Society, Inc. (to C. F. C.), and the Fonds de la Recherches en Santé de Québec (to D. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed: Inst. de Recherches Cliniques de Montréal, 110 Ave. des Pins, Ouest, Montréal, Québec H2W 1R7, Canada. Fax: 514-987-5767; E-mail: lohnesd@ircm.qc.ca.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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