Haldar S, Negrini M, Monne M, Sabbioni S, Croce C M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Cancer Res. 1994 Apr 15;54(8):2095-7.
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.
bcl-2和p53基因产物均与程序性细胞死亡途径相关。我们分析了几种人乳腺癌细胞系中bcl-2和p53的表达情况。我们发现这两种蛋白的表达呈负相关。结果表明，突变型p53可以替代乳腺癌细胞中bcl-2的功能，并且还可以下调bcl-2的表达。实际上，我们发现MCF-7细胞中突变型p53（mut 175）的过表达可在蛋白质和mRNA水平上诱导bcl-2的下调。然而，人bcl-2基因的启动子区域不包含负责下调的负调控元件。如果这种机制也被证明适用于野生型p53等位基因，那么它可能揭示了p53诱导细胞凋亡的一种可能机制：bcl-2的下调。
