Induction of retinoic acid receptor-β suppresses cyclooxygenase-2 expression in esophageal cancer cells

Since retinoic acid receptor (RAR)-β mRNA is frequently lost during esophageal carcinogenesis and esophageal cancer cells that do not express RAR-β are resistant to retinoic acid (RA), we stably transfected RAR-β expression vector into an esophageal cancer cell line TE-8 and an antisense RAR-β into TE-3 cells. Transfection of RAR-β decreased cell growth and colony formation and induced apoptosis in TE-8 cells. Antisense RAR-β-transfected TE-3 cells had a shorter doubling time and became resistant to RA. Induction of RAR-β decreased COX-2 expression in RAR-β transfected TE-8 cells, whereas antisense RAR-β transfected TE-3 cells increased COX-2 expression. The inhibitory effect of RAR-β on COX-2 expression was further enhanced in the presence of RA, which was blocked by an RAR antagonist. The synthetic retinoid N-(4-hydroxyphenyl)retinamide, which does not bind effectively to RAR-β, had no effect on COX-2 suppression. Furthermore, RA blocked bile acid-induced COX-2 expression and prostaglandin E₂ production only in the RAR-β positive cells. Our data demonstrated that anticancer effect of RAR-β may be related to its ability to suppress COX-2 expression and support that the loss of RAR-β expression may contribute to esophageal carcinogenesis.