Characterization of retinoic acid receptor-deficient keratinocytes

Citation
P. Goyette et al., Characterization of retinoic acid receptor-deficient keratinocytes, J BIOL CHEM, 275(22), 2000, pp. 16497-16505
Citations number
76
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
22
Year of publication
2000
Pages
16497 - 16505
Database
ISI
SICI code
0021-9258(20000602)275:22<16497:CORARK>2.0.ZU;2-T
Abstract
Retinoids are essential for normal epidermal growth and differentiation and show potential for the prevention or treatment of various epithelial neopl asms. The retinoic acid receptors (RAR alpha, -beta, and -gamma) are transd ucers of the retinoid signal. The epidermis expresses RAR gamma and RAR alp ha, both of which are potential mediators of the effects of retinoids in th e epidermis. To further investigate the role(s) of these receptors, we deri ved transformed keratinocyte lines from wild-type, RAR alpha RAR gamma, and RAR alpha gamma null mice and investigated their response to retinoids, in cluding growth inhibition, markers of growth and differentiation, and AP-1 activity. Our results indicate that RAR gamma is the principle receptor con tributing to all-trans-retinoic acid (RA)-mediated growth arrest in this sy stem. 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 Rtl 9-cis RA, or the syntheti c retinoid (E)-4-[2-(5, 5, 8, 8 tetramethyl-5,6,7,8-tetrahydro-2- naphthale nyl)-1-propenyl] benzoic acid. Finally, both RAR alpha and RAR gamma differ ently affected the expression of some genes suggesting both specific and ov erlapping roles for the RARs in keratinocytes.