Cellular Origin of Breast Tumors With Invasive Potential

摘要

A major problem in breast cancer treatment and the leading cause of mortality is invasion and metastasis of primary breast tumors. The cell type from which the tumor arises may dictate its potential for aggressive behavior. The mammary gland consists of different cell types including the cap cell; a less differentiated, highly proliferative cell basally located in the terminal end bud (TEB) of the murine mammary gland. The TEBs invade the fatty stroma of the pubertal gland establishing the ductal network. These specialized structures are reported to be targets for carcinogen-induced DNA damage. Their human counterparts are called intralobular ducts and are also sites of cancerous lesions. We hypothesize that genetic change specific to the cap cell population of the TEB will lead to aggressive tumors and metastatic disease. P- cadherin is normally expressed in the cap cells of the TEB and its progenitors. To test whether the less differentiated Pcadherin-positive cells have greater metastatic potential, the neu/HER-2 proto-oncogene will be targeted specifically to the cap cell population using the endogenous P-cadherin promoter. The goal of this research is to determine whether the highly proliferative and invasive cap cell population is a target for metastatic breast cancer.