Abstract
Background: Peroxisome proliferator-activated receptor gamma (PPARγ) is overexpressed in many types of cancer, including breast cancer, and it is regulated by ligand binding and post-translational modifications. It was previously demonstrated that endogenous transactivation promotes an aggressive phenotype of malignant breast cells. This study examines whether selective antagonism of PPARγ with T0070907 is a potential strategy for breast cancer therapy. Materials and Methods: PPARγ activation was inhibited using both pharmacological and molecular approaches and proliferation, apoptosis, migration and invasion were measured in MDA-MB-231 and MCF-7 breast cancer cells. Results: T0070907 treatment inhibited proliferation, invasion and migration but did not significantly affect apoptosis. Molecular inhibition using a dominant negative (Δ462) receptor yielded similar results. T007 also mediated a dose-dependent decrease in phosphorylation of PPARγ, and its ability to bind to DNA, and may directly affect mitogen-activated protein kinase signaling. Conclusion: These data indicate that inhibiting endogenous PPARγ signaling may be a promising new approach to breast cancer therapy.
Original language | English |
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Pages (from-to) | 813-823 |
Number of pages | 11 |
Journal | Anticancer Research |
Volume | 31 |
Issue number | 3 |
State | Published - Mar 2011 |
Keywords
- Breast cancer
- Invasion
- Migration
- PPARG
- PPARγ
- T0070907
ASJC Scopus subject areas
- Oncology
- Cancer Research