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Foreman JE , Chang WCL , Palkar PS , Zhu BK , Borland MG , Williams JL , Kramer LR , Clapper ML , Gonzalez FJ , Peters JM
Functional Characterization of Peroxisome Proliferator-Activated Receptor-beta/delta Expression in Colon Cancer
Molecular Carcinogenesis. 2011 Nov;50(11) :884-900
AbstractThis study critically examined the role of PPAR beta/delta in colon cancer models. Expression of PPAR beta/delta mRNA and protein was lower and expression of CYCLIN D1 protein higher in human colon adenocarcinomas compared to matched non-transformed tissue. Similar results were observed in colon tumors from Apc(+/Min-FCCC) mice compared to control tissue. Dietary administration of sulindac to Apc(+/Min-FCCC) mice had no influence on expression of PPAR beta/delta in normal colon tissue or colon tumors. Cleaved poly (ADP-ribose) polymerase (PARP) was either increased or unchanged, while expression of 14-3-3 epsilon was not influenced in human colon cancer cell lines cultured with the PPAR beta/delta ligand GW0742 under conditions known to increase apoptosis. While DLD1 cells exhibited fewer early apoptotic cells after ligand activation of PPAR beta/delta following treatment with hydrogen peroxide, this change was associated with an increase in late apoptotic/necrotic cells, but not an increase in viable cells. Stable over-expression of PPAR beta/delta in human colon cancer cell lines enhanced ligand activation of PPAR beta/delta and inhibition of clonogenicity in HT29 cells. These studies are the most quantitative to date to demonstrate that expression of PPAR beta/delta is lower in human and Apc(+/Min-FCCC) mouse colon tumors than in corresponding normal tissue, consistent with the finding that increasing expression and activation of PPAR beta/delta in human colon cancer cell lines inhibits clonogenicity. Because ligand-induced attenuation of early apoptosis can be associated with more late, apoptotic/necrotic cells, but not more viable cells, these studies illustrate why more comprehensive analysis of PPAR beta/delta-dependent modulation of apoptosis is required in the future. (C) 2011 Wiley Periodicals, Inc.
NotesForeman, Jennifer E. Chang, Wen-Chi L. Palkar, Prajakta S. Zhu, Bokai Borland, Michael G. Williams, Jennie L. Kramer, Lance R. Clapper, Margie L. Gonzalez, Frank J. Peters, Jeffrey M. [Ca97999]; [ca124533]; [ca126826]; [ca141029]; [ca 140369]; [ca006927]; [ca129467]; [ca140487] We gratefully acknowledge Dr. Andrew Billin and Dr. Timothy Willson for providing the GW0742, Elaine Kunze, Susan Magargee, and Nicole Bem from the Center for Quantitative Cell Analysis at the Huck Institutes of Life Sciences of The Pennsylvania State University for their technical support with flow cytometry and data analysis, and Daniel Beard from the Penn State Hershey Cancer Institute Tissue Bank for providing the human tissue samples, and the Laboratory Animal Facility and the Genomics Facility at Fox Chase Cancer Center. This work was supported in part by CA97999, CA124533, CA126826, CA141029, CA 140369 (to J.M.P.), CA006927 and CA129467 (to M.L.C.) and CA140487 (to J.L.W.). 51 Wiley-blackwell Malden 833aj