Identification of Cytoplasmic Proteins Interacting with the Mammary Cell Transforming Domain of Ese-1
Final rept. 29 Mar 2006-29 Mar 2009
COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
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The Ets family of transcription factors contains several members that are important components of the cellular pathways leading to tumorigenesis. The Ese-1 gene is an Ets member that is particularly relevant to breast cancer. Ese-1 is located on chromosome 1q32.1, in a region that is amplified in 50 of early breast cancers. Ese-1 mRNA is over-expressed in human breast ductal carcinoma in situ DCIS. We discovered that Ese-1 transforms MCF-12A cells via a novel cytoplasmic mechanism in which a unique 40-amino acid AA, serine- and aspartic acid rich SAR domain is necessary and sufficient for transformation. While the original goal was to identify cytoplasmic partners of the Ese-1 SAR motif that mediate transformation, due to difficulties, we pursued a more productive avenue of investigation. To this end, we have demonstrated that Ese-1 is required to maintain the transformed state of T47D, MCF-7 and ZR-75-1 breast cancer cells, and that it does so via a nuclear mechanism, by regulating cell proliferation.
- Medicine and Medical Research