Retinoic acid downregulates growth, fibronectin and RARα in 3T3 cells: Haras blocks this response and RA metabolism

Abstract

Retinoic acid (RA) reduced growth, fibronectin, and retinoic acid receptor (RARα) in NIH 3T3 cells but not in cells transformed by the Ha-ras oncogene. RA lowered RARα transcript and protein, increased RARβ transcripts, and had no effect on RARγ. H-ras transformation downregulated RAR expression and abolished responsiveness to RA. Ha-ras-transformed cells were as active as normal NIH-3T3 cells in RA uptake but were unable to degrade it to medium oxidation products, so that, paradoxically, the resistant cells accumulated 20–30-fold as much RA as the sensitive cells. RA sensitivity/insensitivity correlated with RA metabolism/lack thereof in 15 cell lines in serum-free medium. These data suggest a relationship between RA inhibition of cell growth and intracellular RA metabolism. J. Cell. Physiol. 173:297–300, 1997. Published 1997 Wiley-Liss, Inc.1 This article is a US Government work and, as such, is in the public domain in the United States of America.