Down-regulation of bcl-2 by p53 in breast cancer cells.
bcl-2 and p53 gene products have been both linked to programmed cell death pathways. We have analyzed several human breast cancer cell lines for the expression of bcl-2 and p53. We found an inverse correlation between the expression of the two proteins. The result suggested that mutant p53 could substitute for bcl-2 function in breast cancer cells and that could also down-regulate bcl-2 expression. We found, indeed, that overexpression of a mutant p53 (mut 175) in MCF-7 cells could induce down-regulation of bcl-2 both at protein and mRNA level. However, the promoter region of the human bcl-2 gene does not contain the negative regulatory element responsible for the down-regulation. If this mechanism will be proved also for the wild-type p53 allele, it may disclose a possible mechanism for p53-induced apoptosis: down-regulation of bcl-2.
Haldar
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Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Negrini
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Monne
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Sabbioni
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Croce
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D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002460:Cell Line; D003062:Codon; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D014162:Transfection; D014407:Tumor Cells, Cultured
D003062:Codon; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases