Rapamycin Inhibits Estrogen-Mediated Transcription in Breast Cancer Cell Lines.

摘要

Breast cancer is the second most common malignancy affecting women in the United States. Approximately 182,000 new cases are diagnosed each year. In 1866 Broca was the first to recognize the heritability of breast and ovarian cancer in certain families. In 1990 transmission of breast cancer was genetically linked to a locus on the long arm of chromosome 17. This was followed by the localization of the genes responsible for site-specific hereditary breast cancer and breast/ovarian cancer tandems, BRCAl and BRCA2. These discoveries led to the important quest to determine how these genes function and what if any role they might play in sporadic (non-hereditary) forms of breast cancer. The types of mutations that have been described in the BRCA genes are consistent with loss of function, a characteristic of tumor suppressor genes. Loss of heterozygosity (LOH) at the BRCA1 locus occurs in approximately 50-70% of sporadic breast and ovarian cancers. LOH at the BRCA2 locus occurs in 30-40% of sporadic breast and ovarian tumors. As with other hereditary tumor suppressor genes (e.g. p53 and APC) it was anticipated that BRCA1 and BRCA2 genes have shown few mutations in non-hereditary breast cancer.