Interaction of BRCA1 and p27Kipl Pathway in Breast Cancer

摘要

Women who have familial breast cancer often have a germline mutation of the breast cancer susceptibility gene known as BRCA1. The function of BRCA1 is not totally understood. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of p27(kipl)(kipl) and BRCA1. The p27kipl is a member of the universal cyclin- dependent kinase inhibitor family. BRCA1 has a number of activities including DNA repair, growth inhibition, and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27kipl. This transactivation is dependent on - the presence of a functional C-terminal transactivation domain. Promoter- deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27(kipl) promoter.