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

226 Citations (Scopus)

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
Externally publishedYes

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Eicosanoid Receptors
Peroxisome Proliferator-Activated Receptors
Cytoplasmic and Nuclear Receptors
Colonic Neoplasms
Neoplasms
Caco-2 Cells
Eicosanoids
Prostaglandin-Endoperoxide Synthases
Cell Line
Colorectal Neoplasms
Rodentia
Mucous Membrane
Anti-Inflammatory Agents
Proteins
Enzymes
Cyclooxygenase 2
Polyps
Pharmaceutical Preparations
Carcinogens

ASJC Scopus subject areas

  • Cancer Research

Cite this

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

The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers. / DuBois, Raymond N.; Gupta, Rajnish; Brockman, Jeffrey; Reddy, Bandaru S.; Krakow, Samuel L.; Lazar, Mitchell A.

In: Carcinogenesis, Vol. 19, No. 1, 01.1998, p. 49-53.

Research output: Contribution to journalArticle

DuBois, RN, Gupta, R, Brockman, J, Reddy, BS, Krakow, SL & Lazar, MA 1998, 'The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers', Carcinogenesis, vol. 19, no. 1, pp. 49-53. https://doi.org/10.1093/carcin/19.1.49
DuBois, Raymond N. ; Gupta, Rajnish ; Brockman, Jeffrey ; Reddy, Bandaru S. ; Krakow, Samuel L. ; Lazar, Mitchell A. / The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers. In: Carcinogenesis. 1998 ; Vol. 19, No. 1. pp. 49-53.
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