Cancer Prevention Research 2, 274, March 1, 2009. Published Online First March 3, 2009;
doi: 10.1158/1940-6207.CAPR-08-0180
© 2009 American Association for Cancer Research
Antitumor Effect of Retinoic Acid Receptor-β2 Associated with Suppression of Cyclooxygenase-2
Shumei Song1,
Baoxiang Guan1,
Taoyan Men2,
Ashraful Hoque1,
Reuben Lotan2 and
Xiao-Chun Xu1
Authors' Affiliations: Departments of 1 Clinical Cancer Prevention and 2 Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Requests for reprints: Xiao-Chun Xu, Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Unit 1360, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-745-2940; Fax: 713-563-5747; E-mail: xxu{at}mdanderson.org.
Retinoic acid receptor-β2 (RAR-β2) is a putative tumor suppressor gene in various cancers. To determine the underlying molecular mechanisms, we transfected RAR-β2 cDNA into esophageal cancer TE-1 and TE-8 cells and found that RAR-β2 suppressed tumor cell growth in vitro and tumor formation in nude mice in TE-8 cells, whereas the stable transfection of RAR-β2 did not restore retinoid sensitivity or inhibit tumor formation in nude mouse in TE-1 cells. Molecularly, we revealed that RAR-β2 antitumor activity was associated with expression and suppression of cyclooxygenase-2 (COX-2) in these tumor cell lines. Moreover, antisense RAR-β2 cDNA induced COX-2 expression in TE-3 cells. Furthermore, when COX-2 expression is first blocked by using antisense COX-2 expression vector, the effect of RAR-β2 is diminished in these tumor cells. In addition, we analyzed expression of RAR-β2 and COX-2 mRNA in tissue specimens and found that RAR-β2 expression is associated with low levels of COX-2 expression in esophageal cancer tissues. Induction of RAR-β2 expression in oral leukoplakia tissues after the patients treated with 13-cis RA correlated with a reduction in COX-2 expression and clinical response. Our findings indicate that some of RAR-β2 antitumor activities are mediated by suppression of COX-2 expression in some of these esophageal cancer cells. After correlating antitumor effect of RAR-β2 with COX-2 expression in the published studies, we also found the association. Thus, further studies will determine whether manipulation of COX-2 expression in different cancers can antagonize RAR-β2 activity.
Key Words: Retinoic acid receptor-β2 • cyclooxygenase-2 • esophageal cancer
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Copyright © 2009 by the American Association for Cancer Research.
