p53 Binds to Estrogen Receptor 1 Promoter in Human Breast Cancer Cells

Abstract

p53 is a tumor suppressor protein that regulates estrogen receptor 1 (ESR1) expression. To investigate the mechanism of ESR1 gene regulation by p53, chromatin immunoprecipitation was applied to assess the binding of p53, DNMT1, HDAC1 and MeCP2 to both silenced ESR1 promoter in MDA-MB-468 cells and active ESR1 promoter in MCF-7 breast cancer cells. The results of chromatin immunoprecipitation experiments showed that p53 protein binds to both unmethylated CpG island of the ESR1 promoter in the ER-positive MCF-7 and the hypermethylated ESR1 promoter in the ER-negative MDA-MB-468 cells. However, repression complex including DNMT1, HDAC1 and MeCP2 is only associated with silenced ESR1 in ER-negative MDA-MB-468 human breast cancer cells. In addition, ectopically expressed wild type p53 failed to reactivate the ESR1 gene in these cells. These results suggest that specific p53 mutations may contribute to loss of estrogen receptor α expression in breast tumors and also support the hypothesis that mutant p53 is likely to impact DNA methylation.

The tumor suppressor Caliban regulates DNA damage-induced apoptosis through p53-dependent and -independent activity

“…43 Others suggest MeCP2 and p53 may have feedback regulation. 44 Our results show that Clbn has a physical interaction with a transcriptional repressor of p53 (our unpublished data). Clbn may export transcription suppressors from nucleus upon DNA damage, releases suppression to p53, which needs more study.…”

Estrogen Receptor Alpha Gene Polymorphisms and Breast Cancer Risk: a Case-control Study with Meta-analysis Combined

“…Besides the E2 levels, the PvuII 'C' allele was also associated with decreased levels of androstenedione (Weiderpass et al, 2000). Based on these observations, we believe that the ESR-α gene polymorphisms may indirectly influence the binding activity to the hormone response element on the target gene by regulating gene expression or receptor function, and then influence the transcriptional regulation of it's downstream genes including TP53 (Rasti et al, 2012), causing the origination of the breast cancer.…”

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

“…4). This result, while unexpected, is not unparalleled, as a number of studies have shown that mutant p53 protein is capable of binding to its target gene sequences and regulating their expression (Pan and Haines, 2000;O'Farrell et al, 2004;Weisz et al, 2007;Chandrachud and Gal, 2009;Perez et al, 2010;Rasti et al, 2012). Since the mutant p53 did not associate with the 14-3-3s promoter in the absence of plakoglobin (SCC9 cells), this suggests a role for plakoglobin in associating p53 with its target gene promoter(s).…”