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
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 wi...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2013/121956 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832545288025276416 |
|---|---|
| author | Jeffrey D. Coleman Jerry T. Thompson Russell W. Smith Bogdan Prokopczyk John P. Vanden Heuvel |
| author_facet | Jeffrey D. Coleman Jerry T. Thompson Russell W. Smith Bogdan Prokopczyk John P. Vanden Heuvel |
| author_sort | Jeffrey D. Coleman |
| collection | DOAJ |
| description | 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 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. |
| format | Article |
| id | doaj-art-22a151066ad641a0a6b0f7bda9b3d314 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-22a151066ad641a0a6b0f7bda9b3d3142025-02-03T07:26:16ZengWileyPPAR Research1687-47571687-47652013-01-01201310.1155/2013/121956121956Role of Peroxisome Proliferator-Activated Receptor β/δ and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer CellsJeffrey D. Coleman0Jerry T. Thompson1Russell W. Smith2Bogdan Prokopczyk3John P. Vanden Heuvel4Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Penn State University, 325 Life Sciences Building, University Park, PA 16802, USADepartment of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Penn State University, 325 Life Sciences Building, University Park, PA 16802, USADepartment of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Penn State University, 325 Life Sciences Building, University Park, PA 16802, USADepartment of Pharmacology, Penn State University, Hershey, PA 17033, USADepartment of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Penn State University, 325 Life Sciences Building, University Park, PA 16802, USAPPARβ/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.http://dx.doi.org/10.1155/2013/121956 |
| spellingShingle | Jeffrey D. Coleman Jerry T. Thompson Russell W. Smith Bogdan Prokopczyk John P. Vanden Heuvel 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 PPAR Research |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://dx.doi.org/10.1155/2013/121956 |
| work_keys_str_mv | AT jeffreydcoleman roleofperoxisomeproliferatoractivatedreceptorbdandbcelllymphoma6inregulationofgenesinvolvedinmetastasisandmigrationinpancreaticcancercells AT jerrytthompson roleofperoxisomeproliferatoractivatedreceptorbdandbcelllymphoma6inregulationofgenesinvolvedinmetastasisandmigrationinpancreaticcancercells AT russellwsmith roleofperoxisomeproliferatoractivatedreceptorbdandbcelllymphoma6inregulationofgenesinvolvedinmetastasisandmigrationinpancreaticcancercells AT bogdanprokopczyk roleofperoxisomeproliferatoractivatedreceptorbdandbcelllymphoma6inregulationofgenesinvolvedinmetastasisandmigrationinpancreaticcancercells AT johnpvandenheuvel roleofperoxisomeproliferatoractivatedreceptorbdandbcelllymphoma6inregulationofgenesinvolvedinmetastasisandmigrationinpancreaticcancercells |