Deciphering the Molecular Mechanisms of Breast Cancer
Annual rept. 1 Mar 2002-28 Feb 2003
WISTAR INST OF ANATOMY AND BIOLOGY PHILADELPHIA PA
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Accumulating evidence indicates that BRCAl is a component of large molecular weight complexes. BARD1-BRCAl is reported to be one such complex containing BRCAl. 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 BARDl-BRCAl-containing complex. We hypothesize that BARD1 plays a role in maintenance of genome stability through its interaction with the BRCAl. We will use biochemical techniques that have been instrumental in increasing our understanding of the transcription machinery, and that have not yet been fully utilized in studies of breast cancer, to isolate the BARDl-BRCAl complex. We intend to identify BRCAl-associated proteins that are altered as the result of mutations in BRCAl protein.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research