Abstract
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.
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Acknowledgements
We thank Timothy Hla for kindly providing COX-2 cDNA, and Maureen E Goode of the Department of Scientific Publications for editing the manuscript.
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Li, M., Song, S., Lippman, S. et al. Induction of retinoic acid receptor-β suppresses cyclooxygenase-2 expression in esophageal cancer cells. Oncogene 21, 411–418 (2002). https://doi.org/10.1038/sj.onc.1205106
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DOI: https://doi.org/10.1038/sj.onc.1205106
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