In-Vivo Characterization of Mammalian Polarity Genes as Novel Tumor Suppressors Involved in Breast Cancer Development and Progression in a Mouse Model

摘要

The purpose of our study is to understand the role of novel polarity regulators mammary gland development and their ability to cooperate with oncogenes in tumorogenesis within this gland. We are using mouse systems as well as an analysis of cell lines to understand the role of a particular gene, Scribble, in this process. So far, I have been able to identify one human breast cancer cell line with little scribble expression. In a normal mouse cell line, comma-1D, we are doing further analysis as to the effects of scribble loss using RNAi technology. We have observed a morphological change, with a loss of e-cadherin, as well as a mild proliferative change in scribble knockdown cells. We have also observed a change in lineage specific cytokeratins in these cells. This data is significant as it possibly demonstrates the role of a polarity gene the differentiation of the breast as well as in tumors with concomitant growth changes to the affected tissue.