Mcl-1 and Bim Balance in HER2-Overexpressing Breast Cancer Cells
Author Information
Author(s): Campone Mario, Noël Bélinda, Couriaud Cécile, Grau Morgan, Guillemin Yannis, Gautier Fabien, Gouraud Wilfried, Charbonnel Catherine, Campion Loïc, Jézéquel Pascal, Braun Frédérique, Barré Benjamin, Coqueret Olivier, Barillé-Nion Sophie, Juin Philippe
Primary Institution: Centre de Recherche en Cancérologie Nantes-Angers - UMR 892 - INSERM/Université de Nantes
Hypothesis
The study investigates the role of anti- and pro-apoptotic Bcl-2 family members in the survival of HER2 overexpressing breast cancer cells.
Conclusion
Targeting the Mcl-1/Bim balance is necessary for inducing cancer cell death in HER2-overexpressing tumors.
Supporting Evidence
- The depletion of Mcl-1 induces apoptosis in HER2-overexpressing breast cancer cells.
- Bim expression is regulated by c-Myc, which is influenced by mTORC1 activity.
- HER2 overexpressing tumors show enrichment for Mcl-1 transcripts.
- Knockdown of Bim reduces cell death induced by Mcl-1 depletion.
- RAD001 treatment decreases Bim expression and mitigates Mcl-1 dependence.
Takeaway
Breast cancer cells that have too much HER2 need a special protein called Mcl-1 to stay alive, and if we can change the balance with another protein called Bim, we can make them die.
Methodology
The study used cell lines to evaluate the impact of various Bcl-2 family proteins on the survival of HER2-overexpressing breast cancer cells through RNA interference and western blot analysis.
Limitations
The study primarily focuses on in vitro models, which may not fully replicate the complexity of in vivo tumor environments.
Statistical Information
P-Value
0.0156
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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