Role of peroxisome proliferator-activated receptor β/δ and B-cell lymphoma-6 in regulation of genes involved in metastasis and migration in pancreatic cancer cells

Jeffrey D. Coleman, Jerry T. Thompson, Russell W. Smith, Bogdan Prokopczyk, John P. Vanden Heuvel

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

PPAR β /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 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 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.

Original languageEnglish (US)
Article number121956
JournalPPAR Research
DOIs
StatePublished - Jun 3 2013

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Peroxisome Proliferator-Activated Receptors
B-Cell Lymphoma
Pancreatic Neoplasms
Neoplasm Metastasis
Matrix Metalloproteinases
Genes
Ligands
Basement Membrane
Small Interfering RNA
Peptide Hydrolases
Transcription Factors
Cell Culture Techniques
Gene Expression
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Pharmacology (medical)

Cite this

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abstract = "PPAR β /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 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 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.",
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Role of peroxisome proliferator-activated receptor β/δ and B-cell lymphoma-6 in regulation of genes involved in metastasis and migration in pancreatic cancer cells. / Coleman, Jeffrey D.; Thompson, Jerry T.; Smith, Russell W.; Prokopczyk, Bogdan; Vanden Heuvel, John P.

In: PPAR Research, 03.06.2013.

Research output: Contribution to journalArticle

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