Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

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

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Berard J, Laboune F, Mukuna M, Masse S, Kothary R, Bradley WE . 1996 FASEB J. 10: 1091–1097

  • Carey M, Smale ST . 2000 Transcriptional regulation in eukaryotes: concepts, strategies, and techniques Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  • Chambon P . 1996 FASEB J. 10: 940–954

  • Clifford JL, Menter DG, Wang M, Lotan R, Lippman SM . 1999 Cancer Res. 59: 14–18

  • De Luca LM . 1991 FASEB J. 5: 2924–2933

  • Dmitrovsky E . 1997 J. Natl. Cancer Inst. 89: 1179–1181

  • Dong Z, Huang C, Brown RE, Ma WY . 1997 J. Biol. Chem. 272: 9962–9970

  • Faria TN, Mendelsohn C, Chambon P, Gudas LJ . 1999 J. Biol. Chem. 274: 26783–26788

  • Farrow DC, Vaughan TL, Hansten PD, Stanford JL, Risch HA, Gammon MD, Chow WH, Dubrow R, Ahsan H, Mayne ST, Schoenberg JB, West AB, Rotterdam H, Fraumeni Jr JF, Blot WJ . 1998 Cancer Epidemiol. Biomarkers Prev. 7: 97–102

  • Funkhouser EM, Sharp GB . 1995 Cancer 76: 1116–1119

  • Gebert JF, Moghal N, Frangioni JV, Sugarbaker DJ, Neel BG . 1991 Oncogene 6: 1859–1868

  • Geradts J, Chen JY, Russell EK, Yankaskas JR, Nieves L, Minna JD . 1993 Cell Growth Differ. 4: 799–809

  • Goldstein SM, Moskowitz MA, Levine L . 1984 Cancer Res. 44: 120–125

  • Gudas LJ . 1992 Cell Growth Differ. 3: 655–662

  • Guo YS, Hellmich MR, Wen XD, Townsend Jr CM . 2001 J. Biol. Chem. 276: 22941–22947

  • Hla T, Neilson K . 1992 Proc. Natl. Acad. Sci. USA 89: 7384–7388

  • Houle B, Rochette-Egly C, Bradley WE . 1993 Proc. Natl. Acad. Sci. USA 90: 985–989

  • Hu L, Crowe D, Rheinwald JG, Chambon P, Gudas LJ . 1991 Cancer Res. 51: 3972–3981

  • Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E, Tanabe T . 1994 Eur. J. Biochem. 221: 889–897

  • Li M, Lotan R, Levin B, Tahara E, Lippman SM, Xu X-C . 2000 Cancer Epidemiol. Biomarker Prev. 9: 545–549

  • Li M, Wu X, Xu XC . 2001 Int. J. Cancer 93: 218–223

  • Lin F, Xiao D, Kolluri SK, Zhang X . 2000 Cancer Res. 60: 3271–3280

  • Liu Y, Lee MO, Wang HG, Li Y, Hashimoto Y, Klaus M, Reed JC, Zhang X . 1996 Mol. Cell. Biol. 16: 1138–1149

  • Lotan R, Xu XC, Lippman SM, Ro JY, Lee JS, Lee JJ, Hong WK . 1995 N. Engl. J. Med. 332: 1405–1410

  • Marnett LJ . 1992 Cancer Res. 52: 557555–557589

  • Mestre JR, Subbaramaiah K, Sacks PG, Schantz SP, Dannenberg AJ . 1997a Ann. NY Acad. Sci. 833: 173–178

  • Mestre JR, Subbaramaiah K, Sacks PG, Schantz SP, Tanabe T, Inoue H, Dannenberg AJ . 1997b Cancer Res. 57: 2890–2895

  • Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM . 1996 Cell 87: 803–809

  • Pfahl M, Chytil F . 1996 Annual Review of Nutrition 16: 257–283

  • Qiu H, Zhang W, El-Naggar AK, Lippman SM, Lin P, Lotan R, Xu XC . 1999 Am. J. Pathol. 155: 1519–1523

  • Seewaldt VL, Johnson BS, Parker MB, Collins SJ, Swisshelm K . 1995 Cell Growth Differ. 6: 1077–1088

  • Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J, Beauchamp RD, DuBois RN . 1997 J. Clin. Invest. 99: 2254–2259

  • Song S, Xu XC . 2001 Biochem. Biophys. Res. Comm. 281: 872–877

  • Souza RF, Shewmake K, Beer DG, Cryer B, Spechler SJ . 2000 Cancer Res. 60: 5767–5772

  • Sporn MB, Roberts AB, Goodman DS . 1994 The Retinoids: biology, chemistry, and medicine 2nd ed Raven Press, New York

    Google Scholar 

  • Subbaramaiah K, Lin DT, Hart JC, Dannenberg AJ . 2001 J. Biol. Chem. 276: 12440–12448

  • Swisshelm K, Ryan K, Lee X, Tsou HC, Peacocke M, Sager R . 1994 Cell Growth Differ. 5: 133–141

  • Tegeder I, Pfeilschifter J, Geisslinger G . 2001 FASEB J. 15: 2057–2072

  • Taketo MM . 1998a J. Natl. Cancer Inst. 90: 1529–1536

  • Taketo MM . 1998b J. Natl. Cancer Inst. 90: 1609–1620

  • Tsujii M, DuBois RN . 1995 Cell 83: 493–501

  • Tsujii M, Kawano S, DuBois RN . 1997 Proc. Natl. Acad. Sci. USA 94: 3336–3340

  • Xu XC, Lotan R . 1999 Handbook of experimental pharmacology Nau H and Blaner WS (eds) Springer: Berlin; New York pp 323–343

    Google Scholar 

  • Xu XC, Liu X, Tahara E, Lippman SM, Lotan R . 1999 Cancer Res. 59: 2477–2483

  • Xu XC, Sneige N, Liu X, Nandagiri R, Lee JJ, Lukmanji F, Hortobagyi G, Lippman SM, Dhingra K, Lotan R . 1997a Cancer Res. 57: 4992–4996

  • Xu XC, Sozzi G, Lee JS, Lee JJ, Pastorino U, Pilotti S, Kurie JM, Hong WK, Lotan R . 1997b J. Natl. Cancer Inst. 89: 624–629

  • Yang-Yen HF, Zhang XK, Graupner G, Tzukerman M, Sakamoto B, Karin M, Pfahl M . 1991 New Biologist 3: 1206–1219

  • Zhang F, Subbaramaiah K, Altorki N, Dannenberg AJ . 1998 J. Biol. Chem. 273: 2424–2428

  • Zimmermann KC, Sarbia M, Weber AA, Borchard F, Gabbert HE, Schror K . 1999 Cancer Res. 59: 198–204

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiao-Chun Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205106

Keywords

This article is cited by

Search

Quick links