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Department of Medicine, The New York Hospital-Cornell Medical Center and Anne Fisher Nutrition Center at Strang Cancer Prevention Center, New York, New York 10021 [K. S., A. J. D.]; Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021 [J. R. M., P. G. S., S. P. S.]; and Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan [T. T., H. I.]
Cyclooxygenase-2 (Cox-2), the inducible form of cyclooxygenase, is up-regulated in tumors and transformed cells. Because this enzyme catalyzes the formation of prostaglandins from arachidonic acid, chemopreventive strategies that suppress its expression could be useful for preventing cancer. We investigated whether retinoids suppressed basal expression of Cox-2 or EGF-mediated induction of Cox-2 in human oral squamous carcinoma cells. Treatment with retinoids [all-trans-retinoic acid (all-trans-RA), 9-cis-RA, 13-cis-RA, and retinyl acetate] suppressed both basal levels of Cox-2 and EGF-mediated induction of Cox-2 protein and synthesis of prostaglandin E2. Retinoids also suppressed the induction of Cox-2 mRNA by EGF. Transient transfection experiments showed that EGF caused about a 100% increase in Cox-2 promoter activity, an effect that was suppressed by retinoids. Levels of epidermal growth factor receptor were unaffected by retinoids. Epidermal growth factor caused a nearly 10-fold increase in mitogen-activated protein kinase activity; this effect was not blocked by retinoids.
1 This work was supported in part by Grant CA68136 from the National Cancer Institute and a grant from the American Institute of Cancer Research. J. R. M. was the recipient of a fellowship award from the Cancer Research Foundation of America.
2 To whom requests for reprints should be addressed, at Division of Digestive Diseases, Room F-231, The New York Hospital-Cornell Medical Center, New York, NY 10021.
Received 1/13/97. Accepted 5/15/97.
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J. R. MESTRE, G. CHAN, F. ZHANG, E. K. YANG, P. G. SACKS, J. O. BOYLE, J. P. SHAH, D. EDELSTEIN, K. SUBBARAMAIAH, and A. J. DANNENBERG Inhibition of Cyclooxygenase-2 Expression: An Approach to Preventing Head and Neck Cancer Ann. N.Y. Acad. Sci., January 1, 1999; 889(1): 62 - 71. [Abstract] [Full Text] [PDF]
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