Down-Regulation of bcl-2 by p53 in Breast Cancer Cells

S Haldar, M Negrini, M Monne, S Sabbioni, CM Croce - Cancer research, 1994 - AACR
S Haldar, M Negrini, M Monne, S Sabbioni, CM Croce
Cancer research, 1994AACR
Abstract 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 …
Abstract
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.
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