The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers

Raymond N. DuBois, Rajnish Gupta, Jeffrey Brockman, Bandaru S. Reddy, Samuel L. Krakow, Mitchell A. Lazar

    Research output: Contribution to journalArticle

    227 Scopus citations

    Abstract

    Continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the relative risk of colorectal cancer in humans and decreases tumor yield in rodents treated with carcinogens. One well documented target for NSAIDs is prostaglandin endoperoxide synthase (cyclooxygenase) and two isoforms of this enzyme have been identified, cycleoxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX enzymes produce eicosanoid products, some of which have recently been shown to activate transcription mediated by the nuclear hormone receptor peroxisome proliferator activated receptor γ (PPARγ), whose expression is largely restricted to adipose tissue. The present study was undertaken to determine if PPARγ was expressed in colonic tumors. PPARγ messenger RNA (mRNA) and protein levels were assayed in colonic tumors and normal adjacent mucosa, as well as in a variety of human colon cancer cell lines. There was a marked increase in PPARγ RNA levels in four out of four of the colonic tumors compared to paired normal mucosa, where little expression of PPARγ was detected. Western blotting analysis showed that PPARγ protein was expressed in four out of five colonic tumor samples. PPARγ was also expressed in a subset of polyps, and in certain human colon cancer cell lines as well. Additionally, we were able to demonstrate that an eicosanoid, 15 deoxy-Δ12,14 PGJ2 transactivated transcription of a PPRE-driven promoter in CaCo-2 cells. Thus, we have shown that PPARγ gene and protein expression is elevated in rodent colon tumors, in selected human colon cancer cell lines and that the PPARγ receptor is functional in CaCo-2 cells. Since PPARγ is a ligand-modulated transcription factor, it may provide a novel target for chemopreventive strategies for colorectal cancer.

    Original languageEnglish (US)
    Pages (from-to)49-53
    Number of pages5
    JournalCarcinogenesis
    Volume19
    Issue number1
    DOIs
    StatePublished - Jan 1998

    ASJC Scopus subject areas

    • Cancer Research

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    DuBois, R. N., Gupta, R., Brockman, J., Reddy, B. S., Krakow, S. L., & Lazar, M. A. (1998). The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers. Carcinogenesis, 19(1), 49-53. https://doi.org/10.1093/carcin/19.1.49