TP53-Status-Dependent Oncogenic EZH2 Activity in Pancreatic Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Mouse Strains and In Vivo Experiments
2.2. Primary PDAC Tissue, Primary PDAC Cells, and Gene-Panel-Sequencing
2.3. Cell Cultivation, Transfection, and Treatment
2.4. RNA Isolation and Quantitative Real-Time PCR (qRT-PCR)
2.5. Protein Harvesting and Western Blotting
2.6. Annexin/Propidium Iodide (PI) Staining
2.7. Immunofluorescence and Immunohistochemistry (IHC)
2.8. Chromatin Immunoprecipitation (ChIP) and RNA-Sequencing
2.9. Statistical Analysis
3. Results
3.1. EZH2 Depletion Does Not Reduce Tumor Progression in Orthotopic PDAC Models
3.2. The TP53-Status Determines EZH2-Dependent Target Gene Regulation
3.3. The Induction of PDAC Cell Apoptosis upon EZH2 Depletion Is Restricted to p53wt Status
3.4. Loss of EZH2 Results in p53wt Stabilization in a CDKN2A-Dependent Manner
3.5. P53wt PDAC Evolving in the Absence of EZH2 Circumvents Induction of the CDKN2A-p53wt Axis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Versemann, L.; Patil, S.; Steuber, B.; Zhang, Z.; Kopp, W.; Krawczyk, H.E.; Kaulfuß, S.; Wollnik, B.; Ströbel, P.; Neesse, A.; et al. TP53-Status-Dependent Oncogenic EZH2 Activity in Pancreatic Cancer. Cancers 2022, 14, 3451. https://doi.org/10.3390/cancers14143451
Versemann L, Patil S, Steuber B, Zhang Z, Kopp W, Krawczyk HE, Kaulfuß S, Wollnik B, Ströbel P, Neesse A, et al. TP53-Status-Dependent Oncogenic EZH2 Activity in Pancreatic Cancer. Cancers. 2022; 14(14):3451. https://doi.org/10.3390/cancers14143451
Chicago/Turabian StyleVersemann, Lennart, Shilpa Patil, Benjamin Steuber, Zhe Zhang, Waltraut Kopp, Hannah Elisa Krawczyk, Silke Kaulfuß, Bernd Wollnik, Philipp Ströbel, Albrecht Neesse, and et al. 2022. "TP53-Status-Dependent Oncogenic EZH2 Activity in Pancreatic Cancer" Cancers 14, no. 14: 3451. https://doi.org/10.3390/cancers14143451