p53, a target of estrogen receptor (ER) α, modulates DNA damage-induced growth suppression in ER-positive breast cancer cells

Crystal E. Berger, Yingjuan Qian, Gang Liu, Hongwu Chen, Xinbin Chen

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

In response to genotoxic stress, the p53 tumor suppressor induces target genes for cell cycle arrest, apoptosis, and DNA repair. Although p53 is the most commonly mutated gene in all human cancers, it is only mutated in about 20% of breast cancers. 70% of all breast cancer cases are estrogen receptor (ER)-positive and express ERα. ER-positive breast cancer generally indicates good patient prognosis and treatment responsiveness with antiestrogens, such as tamoxifen. However, ER-positive breast cancer patients can experience loss or a reduction in ERα, which is associated with aggressive tumor growth, increased invasiveness, poor prognosis, and loss of p53 function. Consistent with this, we found that p53 is a target gene of ERα. Specifically, we found that knockdown of ERα decreases expression of p53 and its downstream targets, MDM2 and p21. In addition, we found that ERα activates p53 transcription via binding to estrogen response element half-sites within the p53 promoter. Moreover, we found that loss of ERα desensitizes, whereas ectopic expression of ERα sensitizes, breast cancer cells to DNA damage-induced growth suppression in a p53-dependent manner. Altogether, this study provides an insight into a feedback loop between ERα and p53 and a biological role of p53 in the DNA damage response in ER-positive breast cancers.

Original languageEnglish (US)
Pages (from-to)30117-30127
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number36
DOIs
StatePublished - Aug 31 2012

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Estrogen Receptors
DNA Damage
Cells
Breast Neoplasms
DNA
Growth
Genes
Tumors
Neoplasms
Estrogen Receptor Modulators
Response Elements
Tamoxifen
Transcription
Cell Cycle Checkpoints
DNA Repair
Estrogens
Repair
Apoptosis
Feedback

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

p53, a target of estrogen receptor (ER) α, modulates DNA damage-induced growth suppression in ER-positive breast cancer cells. / Berger, Crystal E.; Qian, Yingjuan; Liu, Gang; Chen, Hongwu; Chen, Xinbin.

In: Journal of Biological Chemistry, Vol. 287, No. 36, 31.08.2012, p. 30117-30127.

Research output: Contribution to journalArticle

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