Deciphering the Molecular Mechanism of Breast Cancer
Annual rept. 1 Mar 2003-28 Feb 2004
PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
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Accumulating evidence indicates that BRCA1 is a component of large molecular weight complexes. BARD1-BRCA1 is reported to be one such complex containing BRCA1. To date, there has been no attempt to purify BARD1-containing complexes. Biochemical purification can yield valuable insights into the polypeptide composition and the functional role of multiprotein complexes. Although the genetic approaches have been successful in defining the genes that are mutated in breast cancer, functional understanding of the protein product of these genes requires biochemical studies. Biochemical - analysis of the gene products of BARD1, BRCA1 and BRCA2 will not only reveal their normal cellular function but also indicate the functional defects associated with the mutated proteins. Although such biochemical approaches have not been applied to studies of breast cancer, they have been successfully utilized in understanding complex cellular processes such as transcriptional regulation. We will isolate and functionally define the BARD-BRCA1-containing complex. We hypothesize that BARD1 plays a role in maintenance of genome stability through its interaction with the BRCA1. We will use biochemical techniques that have been instrumental in increasing our understanding of the transcriptional machinery, and that have not yet been fully utilized in studies of breast cancer, to isolate the BARD1-BRCA1 complex. We intend to identify BRCA1-associated proteins that are altered as the result of mutations in BRCA1 protein.
- Anatomy and Physiology
- Medicine and Medical Research