BIOMEDICINE: An Ounce of Prevention

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Science  25 Oct 2002:
Vol. 298, Issue 5594, pp. 705e-707e
DOI: 10.1126/science.298.5594.705e

The nuclear hormone receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) is the molecular target of the thiazolidinediones, a group of diabetes drugs that activate its function. PPAR-γ is also implicated in tumorigenesis, but whether its activation prevents or promotes cancer has been a matter of controversy.

The results of two new studies support the hypothesis that PPAR-γ activation suppresses tumor formation. Girnun et al. show that mice lacking one copy of the PPAR-γ gene are more prone to develop colonic tumors in response to a chemical carcinogen than are wild-type mice. This effect was not seen when the mice carried mutations in the APC (adenomatous polyposis coli) tumor suppressor gene, suggesting that PPAR-γ prevents tumor initiation. In independent work, Heaney et al. studied PPAR-γ in a class of benign pituitary tumors that can be life-threatening because they secrete high levels of adrenocorticotrophic hormone. Activators of PPAR-γ were found to inhibit growth of human corticotroph tumor cells in culture and prevent development of these tumors in mice. Thus, the clinical utility of the thiazolidinediones could conceivably extend beyond the treatment of diabetes to cancer prevention. — PAK

Proc. Natl. Acad. Sci. U.S.A 99, 13771 (2002); Nature Med. 10.1038/nm784 (2002).

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