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Cancer Research 66, 11975, December 15, 2006. doi: 10.1158/0008-5472.CAN-06-1529
© 2006 American Association for Cancer Research

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Endocrinology

Peroxisome Proliferator-Activated Receptor {gamma} Is a Zac Target Gene Mediating Zac Antiproliferation

Thomas Barz, Anke Hoffmann, Markus Panhuysen and Dietmar Spengler

Molecular Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany

Requests for reprints: Dietmar Spengler, Molecular Neuroendocrinology, Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. Phone: 49-89-30622-559; Fax: 49-89-30622-605; E-mail: spengler{at}mpipsykl.mpg.de.

Zac is a C2H2 zinc finger protein, which regulates apoptosis and cell cycle arrest through DNA binding and transactivation. During tumorigenesis and in response to mitogenic activation, Zac gene expression is down-regulated in a methylation-sensitive manner. As yet, no target genes have been identified that could explain the potent antiproliferative function of Zac. Here, applying genome-wide expression analysis, we identify peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) as a new bona fide Zac target gene, which is induced by direct Zac binding to the proximal PPAR{gamma}1 promoter. We show that in human colon carcinoma cells, ZAC activates expression of PPAR{gamma} target genes in a PPAR{gamma}-dependent manner. Moreover, we show that treatment of pituitary tumor cells with octreotide, a somatostatin analogue, leads to Zac induction and subsequent Zac-dependent up-regulation of PPAR{gamma}, which thereupon mediates part of the antiproliferative activity of Zac. Our work provides a first step toward elucidating a functional relationship between Zac and PPAR{gamma} that could be relevant to the understanding of tumorigenesis and diabetes as well. (Cancer Res 2006; 66(24): 11975-82)




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2006 by the American Association for Cancer Research.