Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation
Peroxisome proliferator-activated receptorδ (PPARδ) regulates a multiplicity of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes likely create risk factors associated with the ability of PPARδ agonists to promote t...
| Main Authors: | , , , , , , |
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| פורמט: | Article |
| שפה: | English |
| יצא לאור: |
Hindawi Limited
2010-01-01
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| סדרה: | PPAR Research |
| גישה מקוונת: | http://dx.doi.org/10.1155/2010/571783 |
| _version_ | 1827089724494315520 |
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| author | Claire B. Pollock Olga Rodriguez Philip L. Martin Chris Albanese Xin Li Levy Kopelovich Robert I. Glazer |
| author_facet | Claire B. Pollock Olga Rodriguez Philip L. Martin Chris Albanese Xin Li Levy Kopelovich Robert I. Glazer |
| author_sort | Claire B. Pollock |
| collection | DOAJ |
| description | Peroxisome proliferator-activated receptorδ (PPARδ) regulates a multiplicity of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes likely create risk factors associated with the ability of PPARδ agonists to promote tumorigenesis in some organs. In the present study, we describe a new gastric tumor mouse model that is dependent on the potent and highly selective PPARδ agonist GW501516 following carcinogen administration. The progression of gastric tumorigenesis was rapid as determined by magnetic resonance imaging and resulted in highly metastatic squamous cell carcinomas of the forestomach within two months. Tumorigenesis was associated with gene expression signatures indicative of cell adhesion, invasion, inflammation, and metabolism. Increased PPARδ expression in tumors correlated with increased PDK1, Akt, β-catenin, and S100A9 expression. The rapid development of metastatic gastric tumors in this model will be useful for evaluating preventive and therapeutic interventions in this disease. |
| first_indexed | 2025-03-20T05:29:04Z |
| format | Article |
| id | doaj.art-88b51a38a8d74c59855dc92b40531fb3 |
| institution | Directory Open Access Journal |
| issn | 1687-4757 1687-4765 |
| language | English |
| last_indexed | 2025-03-20T05:29:04Z |
| publishDate | 2010-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj.art-88b51a38a8d74c59855dc92b40531fb32024-10-03T05:24:00ZengHindawi LimitedPPAR Research1687-47571687-47652010-01-01201010.1155/2010/571783571783Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ ActivationClaire B. Pollock0Olga Rodriguez1Philip L. Martin2Chris Albanese3Xin Li4Levy Kopelovich5Robert I. Glazer6Department of Oncology, Lombardi Comprehensive Cancer Center, Washington, DC 20057, USADepartment of Oncology, Lombardi Comprehensive Cancer Center, Washington, DC 20057, USACenter for Advanced Preclinical Research, SAIC/NCI-Frederick, Frederick, MD 21702, USADepartment of Oncology, Lombardi Comprehensive Cancer Center, Washington, DC 20057, USADepartment of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center, Washington, DC 20057, USAChemoprevention Agent Development and Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20814, USADepartment of Oncology, Lombardi Comprehensive Cancer Center, Washington, DC 20057, USAPeroxisome proliferator-activated receptorδ (PPARδ) regulates a multiplicity of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes likely create risk factors associated with the ability of PPARδ agonists to promote tumorigenesis in some organs. In the present study, we describe a new gastric tumor mouse model that is dependent on the potent and highly selective PPARδ agonist GW501516 following carcinogen administration. The progression of gastric tumorigenesis was rapid as determined by magnetic resonance imaging and resulted in highly metastatic squamous cell carcinomas of the forestomach within two months. Tumorigenesis was associated with gene expression signatures indicative of cell adhesion, invasion, inflammation, and metabolism. Increased PPARδ expression in tumors correlated with increased PDK1, Akt, β-catenin, and S100A9 expression. The rapid development of metastatic gastric tumors in this model will be useful for evaluating preventive and therapeutic interventions in this disease.http://dx.doi.org/10.1155/2010/571783 |
| spellingShingle | Claire B. Pollock Olga Rodriguez Philip L. Martin Chris Albanese Xin Li Levy Kopelovich Robert I. Glazer Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation PPAR Research |
| title | Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation |
| title_full | Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation |
| title_fullStr | Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation |
| title_full_unstemmed | Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation |
| title_short | Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation |
| title_sort | induction of metastatic gastric cancer by peroxisome proliferator activated receptorδ activation |
| url | http://dx.doi.org/10.1155/2010/571783 |
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