Ets1 Regulation of the Small Heat Shock Protein alphaB-Crystallin and Involvement in Breast Cancer Cell TransformationPublic Deposited
The small heat shock protein αB-crystallin is expressed primarily in lens and muscle tissue, but it is also found in lung, kidney and many cancers. Regulators of αB-crystallin have been identified almost exclusively using mouse muscle and lens specific models. It has been well documented that αB-crystallin is expressed in multiple cancers and that its expression correlates with poor prognosis. More specifically, it is commonly expressed in the poor prognosis basal-like breast tumor subtype and its expression correlates with resistance to neo-adjuvant chemotherapy and an invasive phenotype in breast cancer. This study worked to develop a better understanding of the transcriptional regulators of αB-crystallin in breast cancer. A bioinformatics analysis of the human αB-crystallin promoter revealed a putative binding site for the Ets1 transcription factor. Ets1 is the founding member of the ETS-family of transcription factors, and its expression in breast tumors correlates with poor prognosis. Furthermore, Ets1 expression correlates with the basal-like phenotype in breast cancer cell lines making the potential regulation of αB-crystallin by Ets1 a plausible hypothesis. Here we show using a human αB-crystallin reporter system, gel shift analysis, chromatin immunoprecipitation and siRNA technology that Ets1 regulates human αB-crystallin gene expression in breast cancer cell lines. Furthermore, we probed the role of Ets1 in regulating migration, invasion, proliferation and anchorage-independent growth in breast cancer cell lines. Our results provide evidence for Ets1 regulation of αB-crystallin and suggest a highly context dependent role for Ets1 in regulating a motile or transformed phenotype in breast cancer cell lines.