Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Cell Lines
2.3. Clonogenic Assays
2.4. Western Blotting
2.5. MTS Assay
2.6. HRR Assay
2.7. Quantitative Reverse Transcription PCR
2.8. Wound Healing Assay
2.9. Statistics
3. Results
3.1. TGFβ Induces Mesenchymal Morphology in Ovarian Cancer Cells
3.2. TGFβ Alters Expression of EMT Markers in PEO1 and PEO4
3.3. TGFβ Downregulates HR Proteins in BRCA2 WT Cells and Sensitizes Them to Olaparib
3.4. EMT Also Sensitizes Ovarian Cancer Cells to PARP Inhibition
3.5. EMT Alters HR Gene Expression
3.6. EMT Induces an Alternate DNA Repair Pathway and Opens an Additional Therapeutic Window
3.7. TGFB1 and BRCA2 Are Inversely Correlated in Ovarian Carcinoma Patient Samples
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Roberts, C.M.; Rojas-Alexandre, M.; Hanna, R.E.; Lin, Z.P.; Ratner, E.S. Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib. Cancers 2023, 15, 3919. https://doi.org/10.3390/cancers15153919
Roberts CM, Rojas-Alexandre M, Hanna RE, Lin ZP, Ratner ES. Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib. Cancers. 2023; 15(15):3919. https://doi.org/10.3390/cancers15153919
Chicago/Turabian StyleRoberts, Cai M., Mehida Rojas-Alexandre, Ruth E. Hanna, Z. Ping Lin, and Elena S. Ratner. 2023. "Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib" Cancers 15, no. 15: 3919. https://doi.org/10.3390/cancers15153919
APA StyleRoberts, C. M., Rojas-Alexandre, M., Hanna, R. E., Lin, Z. P., & Ratner, E. S. (2023). Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib. Cancers, 15(15), 3919. https://doi.org/10.3390/cancers15153919