NDLI: Transcriptional Regulation of Estrogen Receptor-α by p53 in Human Breast Cancer Cells

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Transcriptional Regulation of Estrogen Receptor-α by p53 in Human Breast Cancer Cells

Content Provider	PubMed Central
Author	Shirley, Stephanie Harkey Rundhaug, Joyce E. Tian, Jie Cullinan-ammann, Noirin Lambertz, Isabel Conti, Claudio J. Robin, Fuchs-young
Abstract	Estrogen receptor α (ER) and p53 are critical prognostic indicators in breast cancer. Loss of functional p53 is correlated with poor prognosis, ER negativity and resistance to antiestrogen treatment. Previously, we found that p53 genotype was correlated with ER expression and response to tamoxifen in mammary tumors arising in MMTV-Wnt-1 transgenic mice. These results lead us to hypothesize that p53 may regulate ER expression. To test this, MCF-7 cells were treated with doxorubicin or ionizing radiation, both of which stimulated a 5-fold increase in p53 expression. ER expression was also increased 4-fold over a 24 hour time frame. In cells treated with siRNA targeting p53, expression of both p53 and ER was significantly reduced (>60%) by 24 hours. Induction of ER by DNA-damaging agents was p53-dependent as either IR or dox failed to upregulate ER after treatment with p53-targeting siRNA. To further investigate whether p53 directly regulates transcription of the ER gene promoter, MCF-7 cells were transiently transfected with a wild type (WT) p53 expression vector along with a luciferase reporter containing the proximal promoter of ER. In cells transfected with WT p53, transcription from the ER promoter was increased 8-fold. Chromatin immunoprecipitation assays showed that p53 was recruited to the ER promoter along with CARM1, CBP, c-Jun and Sp1 and that this multifactor complex was formed in a p53-dependent manner. These data demonstrate that p53 regulates ER expression through transcriptional control of the ER promoter, accounting for their concordant expression in human breast cancer.
Related Links	http://dx.doi.org/10.1158/0008-5472.CAN-08-3628
Starting Page	3405
File Format	PDF
ISSN	15387445
e-ISSN	15387445
Journal	Cancer research
Issue Number	8
Volume Number	69
Language	English
Publisher Date	2009-04-15
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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