The expression of retinoid X receptor genes is regulated by all-trans- 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 RAR alpha, -beta, and -gamma 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 RXR alpha and 3.8-kb RXR gamma mRNAs, decreased the amounts of 2.3-kb RXR gamma mRNA, but had no significant effect on the levels of RXR beta 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 RXR alpha and 3.8-kb RXR gamma 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 RXR alpha 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 RXR gamma mRNA, suggesting that ongoing protein synthesis was required for the regulation of RXR gamma 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.
Wan
Y J
YJ
Department of Pathology, Harbor-UCLA Medical Center, Torrance 90509.
Wang
L
L
Wu
T C
TC
D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013237:Stereoisomerism; D018243:Teratocarcinoma / Q000235:genetics*; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014212:Tretinoin; D000242:Cyclic AMP