Biological and Genetic Analysis of a New Model for Breast Premalignancy

摘要

The goal of this project was to gain further understanding of premalignant hyperplasia and its role in progression to breast cancer. Most human and mouse model breast cancer research has focused on tumors and metastsis, whereas the biology of premalignant lesions has not been thoroughly studied. We established a new mouse model of premalignant hyperplasia using six serially transplantable, stable, hyperplastic outgrowth cell lines to analyze neoplastic lesions within the intact microenvironment of the mammary gland. These cell lines were ideally suited to DNA micro array to identity changes in gene expression between premalignant cells growing in the mammary gland and tumors that arise from these tissues. Our studies have defined genes differentially expressed in the transition from normal to premalignant mammary disease as well as from premalignant to malignant mammary cancer. The genes related to the malignant transition in our system have also been identified as potential regulators of human breast cancer. The lines developed in this study can be utilized to develop chemoprevention and therapeutic protocols for breast cancer in the future.