ESE-1 is Required to Maintain the Transformed Phenotype of MCF-7 and ZR-75-1 Human Breast Cancer Cells

Background: ETS factors comprise a large transcription factor family known to play a significant role in cellular development, differentiation, and transformation. The human Epithelial Specific Ets factor-1, ESE-1, is particularly relevant in breast cancer. Specifically, increased mRNA expression of ESE-1 and the Her2/neu protooncogene are correlated in breast cancer, and activation of the Her2/Neu receptor induces ESE-1 gene transcription. Stable expression of ESE-1 initiated transformation of ESE-1-negative MCF-12A immortalized human mammary epithelial cells, leading to increased migration, invasion and anchorage independent growth. However, little is known about ESE-1 protein expression and its role in maintaining the transformed phenotype in human breast cancer cell lines. Results: Here, we used an anti-ESE-1 mouse monoclonal antibody in Western blot and immunofluorescent cell analyses to show that ESE-1 is expressed as a nuclear protein in MCF-7, T47D and ZR-75-1 transformed, tumorigenic mammary epithelial cell lines, and that it is not expressed in transformed MDA-MB-231 and nontransformed MCF-10A and MCF-12A cells. In addition, specific knockdown of endogenous ESE-1 in the human breast carcinoma ZR-75-1 and MCF-7 cell lines decreased colony formation and anchorage independent growth. Mechanistically, ESE-1 knockdown decreased cellular proliferation, but had no effect on apoptosis. Conclusions: These results establish that the knockdown of a single ETS factor, ESE-1, is sufficient to reverse the transformed phenotype in breast cancer and demonstrate that ESE-1 is required for cellular proliferation. Thus, ESE-1 plays a key role in maintaining the transformed phenotype in breast cancer, providing a novel single-point target for therapy.