Regulation of estrogen receptor-α expression by the tumor suppressor gene p53 in MCF-7 cells
Regulation of estrogen receptor-α expression by the tumor suppressor gene p53 in MCF-7 cells
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DOI：
10.1677/joe.0.1800497
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发表时间：
2004-03-01
影响因子：
4
通讯作者：
Saceda, M
中科院分区：
文献类型：
--
作者：
Angeloni, SV;Martin, MB;Saceda, M
此处介绍的结果表明，p53上调人类乳腺癌细胞系MCF-7中的雌激素受体-Alpha（Eralpha）表达。使用两种方法来改变细胞中p53的活性。在第一种方法中，建立了表达反义p53的稳定转染物。在稳定的克隆中，反义p53的表达导致eralpha蛋白的表达降低。在第二种方法中，MCF-7细胞用野生型p53瞬时转染。 p53的过表达增加了eralpha的量。为了确定p53对eralpha表达的影响是否是由于转录的变化，使用了eralpha启动子的缺失突变体。这种实验方法表明，p53通过通过位于启动子A上游的元素增加基因的转录来上调Eralpha基因表达。使用p53突变体的转染测定进一步表明，p53诱导的Eralpha基因转录的增加不依赖p53与DNA结合，但与其他蛋白质相互作用的能力。
The results presented here demonstrate that p53 upregulates estrogen receptor-alpha (ERalpha) expression in the human breast cancer cell line MCF-7. Two approaches were used to alter the activity of p53 in the cells. In the first approach, stable transfectants expressing an antisense p53 were established. In the stable clones, expression of antisense p53 resulted in a decrease in the expression of ERalpha protein. In the second approach, MCF-7 cells were transiently transfected with wild-type p53. Overexpression of p53 increased the amount of ERalpha. To determine whether the effects of p53 on the expression ERalpha were due to changes in transcription, deletion mutants of the ERalpha promoter were used. This experimental approach demonstrated that p53 up-regulates ERalpha gene expression by increasing transcription of the gene through elements located upstream of promoter A. Transfection assays using p53 mutants further demonstrated that the p53-induced increase in ERalpha gene transcription was not dependent on the ability of p53 to bind to DNA but on its ability to interact with other proteins.