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 language | English (US) |
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Pages (from-to) | 63-70 |
Number of pages | 8 |
Journal | Breast Cancer Research and Treatment |
Volume | 119 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2010 |
Keywords
- Basal-like breast cancer
- Ets1
- Gene regulation
- Molecular chaperone
- αB-crystallin
ASJC Scopus subject areas
- Oncology
- Cancer Research