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PPAR Research
Volume 2013 (2013), Article ID 121956, 11 pages
Research Article

Role of Peroxisome Proliferator-Activated Receptor and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells

1Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Penn State University, 325 Life Sciences Building, University Park, PA 16802, USA
2Department of Pharmacology, Penn State University, Hershey, PA 17033, USA
3Penn State Cancer Institute, Hershey, PA 17033, USA
4Indigo Biosciences Inc., State College, PA 16801, USA

Received 9 January 2013; Revised 18 March 2013; Accepted 7 April 2013

Academic Editor: Annamaria Cimini

Copyright © 2013 Jeffrey D. Coleman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


PPAR / is a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor, BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis that PPAR / is expressed in human pancreatic cancer cells and that its activation could regulate MMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression of MMP-9 and PPAR / , and lower levels of BCL-6 mRNA. PPAR / activation reduced the TNFα-induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors of PPAR / , BCL-6, and MMP-9, it was evident that PPAR / was responsible for the ligand-dependent effects whereas BCL-6 dissociation upon GW501516 treatment was ultimately responsible for decreasing MMP-9 expression and hence invasion activity. These results suggest that PPAR / plays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release of BCL-6 and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.