Regulation of αB-crystallin gene expression by the transcription factor Ets1 in breast cancer

Joshua D. Bosman, Fruma Yehiely, Joseph R. Evans, Vincent L. Cryns

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Recent studies indicate that the small heat shock protein αB-crystallin is expressed in poor prognosis basal-like breast tumors and likely contributes to their aggressive phenotype. However, the mechanisms underlying the deregulated expression of αB-crystallin in basal-like tumors are poorly understood. Using a bioinformatics approach, we identified a putative DNA binding motif in the human αB-crystallin promoter for the proto-oncogene Ets1, a member of the ETS transcription factor family that bind to DNA at palindromic ETS-binding sites (EBS). Here we demonstrate that ectopic expression of Ets1 activates the αB-crystallin promoter by an EBS-dependent mechanism and increases αB-crystallin protein levels, while silencing Ets1 reduces αB-crystallin promoter activity and protein levels. Chromatin immunoprecipitation analyses showed that endogenous Ets1 binds to the αB-crystallin promoter in basal-like breast cancer cells in vivo. Interrogation of publically available gene expression data revealed that Ets1 is expressed in human basal-like breast tumors and is associated with poor survival. Collectively, our results point to a previously unrecognized link between the oncogenic transcription factor Ets1 and αB-crystallin in basal-like breast cancer.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalBreast Cancer Research and Treatment
Volume119
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Basal-like breast cancer
  • Ets1
  • Gene regulation
  • Molecular chaperone
  • αB-crystallin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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