Molecular Biology Reports

, Volume 38, Issue 2, pp 833–840 | Cite as

All-trans- and 9-cis-retinoic acids activate the human cyclooxynase-2 gene: a role for DR1 as RARE or RXRE



The human COX-2 promoter contains a direct repeat 1 (DR1) which was shown to confer responsiveness to PPARs. We found that in AN3CA and F9 cells, this hCOX-2 DR1 mediates responsiveness to all-trans-retinoic acid (tRA) or 9-cis-retinoic acid (9cRA), but this effect was suppressed by PPARδ. Truncated PPARδ lacking the activation domain AF2 cannot suppress RA-induced activation of the hCOX-2 gene via DR1, suggesting that cofactor recruitment by AF2 is required for the suppression by PPARδ. Gel shift assay showed that PPAR/RXR, RARβ/RXR, and RXR/RXR, bind to hCOX-2 DR1, revealing the promiscuity of this DR1. Particularly, RXR homodimer was able to bind to this DR1 only in the presence of 9cRA. Our results established that tRA and 9cRA are potent inducers of hCOX-2 and that the hCOX-2 DR1 could either serve as RARE or RXRE depending on cellular contexts.


COX-2 PPARδ RAR RXR DR1 Retinoic acids 





Peroxisome proliferator-activated receptor


Retinoic acid receptor


All-trans-retinoic acid


9-Cis-retinoic acid


Direct repeat 1





This work was supported by National Research Foundation of Korea Grant funded by the Korean Government (313-2008-2-C00642). Authors thank members of the Lim laboratory for various technical supports.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, IBST, RCTCKonkuk UniversitySeoulKorea
  2. 2.Department of Molecular Pharmacology and Experimental TherapeuticsMayo Clinic College of MedicineRochesterUSA

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