Characterized BRCA1 and BRCA2 proteins and screening and therape

Details Characterized BRCA1 and BRCA2 proteins and screening and therape Characterized BRCA1 and BRCA2 proteins and screening and therape

1996-02-20

1999-04-06

Low, Christopher S. F.

Drug, bio-affecting and body treating compositions

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514 44, 4351733, 435325, 435 691, 4351723, 424 9321, 536 231, A61K 4800

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058918574

ABSTRACT:
Genetic analysis of familial breast and ovarian cancer indicates that BRCA1 is a tumor suppressor gene. The BRCA1 gene encodes a 190 kDa protein with sequence homology and biochemical analogy to the granin family of proteins. Granins are secreted from endocrine cells via the regulated secretory pathway and are proteolytically cleaved to yield biologically active peptides. BRCA1 protein localizes to secretory vesicles, and was demonstrated to be secreted. Gene transfer of BRCA1 inhibits growth and tumorigenesis of breast and ovarian cancer cells, but not colon or lung cancer cells or fibroblasts, suggesting that BRCA1 encodes a tissue-specific growth inhibitor. Thus, BRCA1 is a secreted growth inhibitor and functions by a mechanism not previously described for tumor suppressor genes. The BRCA2 breast and ovarian cancer gene encodes a protein that also includes a granin region, indicating that the BRCA2 protein is also a secreted tumor suppressor. Therapeutic methods using the BRCA1 and BRCA proteins and genes are also described. A method of screening for the receptors of the BRCA1 protein and BRCA2 proteins is also described.

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