RARgamma acts as a tumor suppressor in mouse keratinocytes.

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 RARgamma, but not RARalpha, predisposed keratinocytes to v-Ha-Ras-induced squamous cell carcinoma. We also found that ablation of RARgamma, but not RARalpha, 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 RARgamma, in murine keratinocytes.

journal_name

Oncogene

journal_title

Oncogene

authors

Chen CF,Goyette P,Lohnes D

doi

10.1038/sj.onc.1207682

subject

Has Abstract

pub_date

2004-07-08 00:00:00

pages

5350-9

issue

31

eissn

0950-9232

issn

1476-5594

pii

1207682

journal_volume

23

pub_type

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