Bcl2-negative MCF7 cells overexpress p53: implications for the cell cycle and sensitivity to cytotoxic drugs.
OBJECTIVE
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.
Poliseno
Laura
L
Laboratorio di Terapia Genica e Molecolare, Istituto di Fisiologia Clinica, CNR, Area della Ricerca, Via G. Moruzzi, 56124 Pisa, Italy.
Mariani
Laura
L
Collecchi
Paola
P
Piras
Antonio
A
Zaccaro
Lucia
L
Rainaldi
Giuseppe
G
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D019311:Staurosporine; D002945:Cisplatin