Expression of BRCA2 Gene Product in Normal and Breast Cancer Cells and in Vivo Analysis of its Tumor Suppressor Function

摘要

Breast cancer is a major health problem affecting American women, accounting for 181200 new cases diagnosed in 1997 and 17% of all cancer deaths (Parker et al, 1997). Among the various epidemiological factors that contribute to the development of breast cancer, a positive family history of breast cancer in a first degree relative is associated with a doubling of risk (Claus et al, 1990). It has been estimated that genetically inherited forms of breast cancer account for approximately 5%- 10% of all breast cancer cases (Weber and Garber, 1997). Genetic linkage analysis in large kindred's with several affected individuals, has localized two breast cancer susceptibility genes, Brcal (Hall et al, 1990) and Brca2 (Wooster et al, 1994) to the long arm of chromosomes 17q21 and 13q 12 respectively. These two genes have recently been isolated by positional cloning strategies (Miki et al, 1994; Wooster et al, 1995). Germline mutations in Brcal predispose the carrier females to early onset breast and ovarian cancer, while Brca2 mutations increase the susceptibility to breast and pancreatic cancer. Unlike Brcal, mutations in Brca2 also increase the risk of male breast cancer (Stratton et al, 1994). Identification of these 2 breast cancer predisposing genes has enabled the development of diagnostic tools for carrier detection and therapeutic intervention in familial breast cancer.