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PP2A Regulation of Cyclin E in Breast Cancer: Therapeutic Applications
Annual rept. 1 Apr 2011-30 Mar 2012
SANFORD-BURNHAM MEDICAL RESEARCH INST LA JOLLA CA
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Cyclin E is a major determinant in breast cancer initiation, progression, and chemotherapy response. Overexpression of cyclin E1 occurs in approximately 50 of breast cancers and this phenotype is associated with increased tumor aggressiveness, metastasis, hormone-independent growth, and poor patient survival. However, the molecular mechanism responsible for cyclin E alterations in breast cancers is not understood. In this research project, we explore the potential involvement of the protein phosphatase PP2A in causing cyclin E abnormalities in breast cancer. This will be achieved by identifying the PP2A holoenzyme complex that regulates cyclin E, evaluate the effects of PP2A activity knockdown on breast cancer progression, and screen for small molecules that can selectively inhibit PP2A regulation of cyclin E to attempt to correct for these alterations in breast cancers.
APPROVED FOR PUBLIC RELEASE