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PPARβ / δ  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  PPARβ / δ  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  PPARβ / δ , and lower levels of  BCL-6  mRNA.  PPARβ / δ  activation reduced the TNF  α  -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  PPARβ / δ ,  BCL-6 , and  MMP-9 , it was evident that  PPARβ / δ  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  PPARβ / δ  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.

ppar research

Role of Peroxisome Proliferator-Activated Receptor<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi mathvariant="bold-italic">β</mml:mi><mml:mo>/</mml:mo><mml:mi mathvariant="bold-italic">δ</mml:mi></mml:math>and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells

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