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Am J Physiol Gastrointest Liver Physiol 283: G266-G269, 2002; doi:10.1152/ajpgi.00486.2001
0193-1857/02 $5.00
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Vol. 283, Issue 2, G266-G269, August 2002

INVITED REVIEW
Controversy: PPARgamma as a target for treatment of colorectal cancer

Rajnish A. Gupta and Raymond N. Dubois

Departments of Cell Biology and Medicine, Vanderbilt University Medical Center and Veterans Affairs Medical Center, Nashville, Tennessee 37232

Colorectal cancer (CRC) represents a significant cause of morbidity and mortality worldwide. Recently, ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor gamma  (PPARgamma ) have exhibited promise in the treatment of CRC. For example, activation of PPARgamma reduces the proliferation of cultured CRC cells grown in vitro or in vivo using the nude mouse xenograft model of tumor growth. Furthermore, agonists of the receptor also reduce the development of preneoplastic lesions in a model of carcinogen-induced CRC in rats. However, ligands for the receptor paradoxically enhance intestinal adenoma formation in another murine model of intestinal polyposis, the APCMin mice. These disparate results may be due to the inherent limitations of the APCMin mouse as a model for humans with CRC. Finally, genetic studies identifying loss of function mutations of PPARgamma in human CRC specimens strongly suggest a tumor suppressive role for the receptor during the development of CRC.

nuclear hormone receptor; intestinal epithelial cell differentiation


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