Regulation of estrogen receptor-α expression by the tumor suppressor gene p53 in MCF-7 cells

Abstract

The results presented here demonstrate that p53 upregulates estrogen receptor-α (ERα) 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 anti-sense p53 resulted in a decrease in the expression of ERα protein. In the second approach, MCF-7 cells were transiently transfected with wild-type p53. Overexpression of p53 increased the amount of ERα. To determine whether the effects of p53 on the expression of ERα were due to changes in transcription, deletion mutants of the ERα promoter were used. This experimental approach demonstrated that p53 up-regulates ERα 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 ERα gene transcription was not dependent on the ability of p53 to bind to DNA but on its ability to interact with other proteins. © 2004 Society for Endocrinology.