Peroxisome Proliferator-Activated Receptor-γ Suppresses Cyclooxygenase-2 Expression in Human Prostate Cells
- Department of Clinical Cancer Prevention, University of Texas M.D. Anderson Cancer Center, Houston, Texas
- Requests for reprints:
David G. Menter, Department of Clinical Cancer Prevention, Unit 236, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-0626; Fax: 713-794-4403. E-mail: dmenter{at}mdanderson.org
Abstract
Recent studies have found that cyclooxygenase-2 (COX-2) protein expression was low and inducible with cytokines in prostate cancer cells (in the absence of serum) and that, in contrast, COX-2 expression was high in normal prostate epithelial cells (EC). Peroxisome proliferator-activated receptor-γ (PPAR-γ) was expressed at high levels in the prostate cancer cell line PC-3 but not in ECs. In contrast to previous findings by others, PPAR-γ ligands did not induce PPAR-γ expression in EC or PC-3. The present study examined the relationship between PPAR-γ and COX-2 expression patterns in EC and PC-3 in the presence and absence of serum and/or the PPAR-γ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). We also evaluated the effects that the forced expression of PPAR-γ1 and PPAR-γ2 had on COX-2 in ECs. We found that expression of PPAR-γ and COX-2 protein was inversely correlated in ECs and PC-3. Low COX-2 expression in PC-3 was up-regulated by serum, and 15d-PGJ2 blocked serum-induced COX-2 expression and activity in a dose-dependent manner. 15d-PGJ2 had no effect on COX-2 expression in ECs or PPAR-γ expression in either cell type. However, forced expression of PPAR-γ1 or PPAR-γ2 in ECs suppressed the high level of endogenous COX-2. This effect was not isoform specific and was augmented by 15d-PGJ2. The present study showed that PPAR-γ activation can be an important regulator of COX-2 in prostate cells and may be an important target for prostate cancer chemoprevention.
Footnotes
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↵2 V. Subbarayan et al. Differential peroxisome proliferator-activated receptor-γ isoform expression and agonist effect in normal and malignant prostate cells, submitted for publication.
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↵3 V. Subbarayan et al., this issue.
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↵4 V. Subbarayan et al., this issue.
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↵5 V. Subbarayan et al., this issue.
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↵6 V. Subbarayan et al., this issue.
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↵7 V. Subbarayan et al., this issue.
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Grant support: NIH grant 5U10CA37429 and American Cancer Society grant TPRN-99-240-01-CNE-1.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 6, 2004.
- Received February 17, 2003.
- Revision received February 17, 2003.
