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Updated: Jul 2, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Bcl2-negative MCF7 cells overexpress p53: implications for the cell cycle and sensitivity to cytotoxic drugs
Laura Poliseno1, Laura Mariani, Paola Collecchi
1Laboratorio di Terapia Genica e Molecolare, Istituto di Fisiologia Clinica, CNR, Area della Ricerca, Via G. Moruzzi, 56124 Pisa, Italy.
Purpose:
Bcl2 is a mitochondrial protein endowed with cytostatic and antiapoptotic activities. In this work we studied the effects of the lack of Bcl2 in MCF7 cells.
Methods:
The breast cancer cell line MCF7 (Bcl2-positive) and its derivative MCF7/50B (Bcl2-negative) were compared in terms of the level of p53 expression, doubling time and distribution of cells among the cycle phases. Sensitivities to the proapoptotic drugs cisplatinum and staurosporine were measured using a clonogenic assay and the contribution of apoptosis to cytotoxicity was determined with a mitochondrial membrane potential-sensitive dye.
Results:
Relative to MCF7, MCF7/50B cells overexpressed p53 and slowly proliferated with a significant accumulation at G(0)/G(1) and depletion in S phase. The cytotoxicity of the DNA-damaging agent cisplatinum was decreased, while that of the protein kinase inhibitor staurosporine was increased. The induced cytotoxicity was essentially due to apoptosis and necrosis, respectively.
Conclusions:
These results suggest that the lack of Bcl2 accompanied by p53 overexpression affects the distribution of cells among the cell cycle phases and modifies the sensitivity to cytotoxic drugs and the type of cell death.
Insights
The absence of Bcl2 in breast cancer cells, coupled with increased p53, alters cell cycle progression and drug response. This impacts cell death mechanisms, influencing cancer treatment strategies.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Bcl2 is a mitochondrial protein that inhibits apoptosis and promotes cell survival.
- Understanding Bcl2's role is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the functional consequences of Bcl2 absence in MCF7 breast cancer cells.
- To analyze the impact on cell proliferation, cell cycle distribution, and drug-induced cell death.
Main Methods:
- Comparison of Bcl2-positive (MCF7) and Bcl2-negative (MCF7/50B) cells.
- Assessment of p53 expression, cell doubling time, and cell cycle phase distribution.
- Evaluation of drug sensitivity (cisplatin, staurosporine) and cell death mechanisms (apoptosis, necrosis).
Main Results:
- Bcl2-negative cells exhibited p53 overexpression, slower proliferation, and G(0)/G(1) cell cycle accumulation.
- Cytotoxicity to cisplatin decreased, while sensitivity to staurosporine increased.
- Cell death was predominantly apoptotic with cisplatin and necrotic with staurosporine.
Conclusions:
- Bcl2 deficiency and p53 overexpression significantly alter cell cycle dynamics in breast cancer cells.
- The absence of Bcl2 modifies cellular responses to cytotoxic agents, shifting cell death pathways.
- These findings provide insights into Bcl2's role in chemoresistance and cell fate determination.
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