THE EXPRESSION OF RETINOID X RECEPTOR GENES IS REGULATED BY ALL-TRANS-RETINOIC AND 9-CIS-RETINOIC ACID IN F9 TERATOCARCINOMA CELLS

Two classes of nuclear receptors for retinoic acid (RA) have been identified - retinoic acid receptor (RAR) and retinoid x receptor (RXR). Previously, we demonstrated that all-trans-retinoic acid (t-RA) differentially self-regulated the expression of RARα, -β, and -γ transcripts. In the present study, we examined the effect of t-RA and 9-cis-RA (c-RA) on the expression of RXR genes in F9 cells by Northern blot analyses. The results showed that t-RA increased the levels of both the 5.6-kb RXRα and 3.8-kb RXRγ mRNAs, decreased the amounts of 2.3-kb RXRγ mRNA, but had no significant effect on the levels of RXRβ mRNA. Addition of a cyclic AMP analog along with t-RA further induced the differentiation of F9 cells to become parietal endodermal cells, but did not change the regulatory patterns of RXR mRNAs. The RNA synthesis inhibitor, actinomycin D, blocked the induction of 5.6-kb RXRα and 3.8-kb RXRγ mRNA by t-RA, suggesting that the regulations at least in part were at the transcriptional levels. The protein synthesis inhibitor, cycloheximide, induced the expression of 5.6-kb RXRα mRNA and further enhanced the inductive effect of t-RA. In contrast, cycloheximide prevented the t-RA-regulated expression of both 3.8- and 2.3-kb RXRγ mRNA, suggesting that ongoing protein synthesis was required for the regulation of RXRγ gene. In addition, c-RA exerted effects similar to those of t-RA on RXR gene expression. A concentration of 10−8 M was required for c-RA to regulate the expression of RXR genes, while 10−9 M of t-RA was effective in regulating RXR genes. Addition of t-RA and c-RA simultaneously had neither synergistic nor additive effects in regulating RXR gene expression. These data suggest that RAR may play an important role in RA-regulated RXR gene expression. © 1994 Academic Press, Inc.