Construction and Characterization of Human Mammary Epithelial Cell LinesContaining Mutations in the p53 or BRCAl Genes

摘要

The overall goal of this project is to identify and characterize the consequencesof human mammary epithelial cells (HMEC) that become deficient in normal p53 and BRCA1 gene functions. Our work during the third year of the funding period has produced good progress establishing new systems to create and characterize HMEC with an altered tumor suppressor gene activity. In collaboration with Dr. Bissell's laboratory (UC Berkeley), we have established three-dimensional culture system in our laboratory. This system will allow us to see differences of the growth properties, expression and distribution of certain cell lineage markers, morphology and behavior in between normal cells and partially transformed cells. Our recent acquisition of a Microarray Spotting and Scanning instrument enabled us the use of this robust and sensitive microarray technology to establish genetic expression profiles from any cell source of interest. We have also applied the differential display protocol to identify genes with altered expression in a model system of normal and neoplastic epithelial cells. We firmly believe that these new systems will provide us critical information to our understanding of breast carcinogenesis.