Retinoic acid regulates gene expression of retinoic acid receptors alpha, beta and gamma in F9 mouse teratocarcinoma cells.

The regulatory effects of retinoic acid (RA) on retinoic acid receptor (RAR) alpha, beta and gamma mRNA were examined in the F9 mouse teratocarcinoma cells. Northern blot hybridization showed that RA regulated all three types of RAR gene expression. The different transcripts for each RAR alpha and beta were differentially regulated by RA. The maximum induction of the 2.8 kb RAR alpha and 3.3 kb RAR beta transcript levels by RA took longer than the induction of the 3.8 kb RAR alpha and 3.5 kb RAR beta transcript levels. The data suggest that these transcripts originated from different promoters. Short term treatment (< or = 24 hours) of RA induced both 3.1 and 3.3 kb RAR gamma transcripts. Long term treatment (> 24 hours) of RA resulted in the inhibition of 3.1 kb mRNA, whereas the 3.3 kb mRNA remained elevated. In addition, a new RAR gamma transcript of 2.9 kb was induced. In contrast to RAR alpha and beta, the effect on RAR gamma gene expression was irreversible. Cycloheximide did not prevent the effect of RA on RAR gene expression, whereas actinomycin D totally abolished the RA effect on the expression of all three receptor genes. The data suggest that the biological effects of RA may be constrained or augmented by differential regulation of its own receptor gene expression.