Environmentally Induced Gene Silencing in Breast Cancer

Abstract

Abstract : The main goal of the study was to test the hypothesis that a reduction in gene expression (i.e. gene repression) could induce gene silencing (i.e. relatively stable loss of gene expression) in breast cells. Silencing of a variety of tumor suppressor genes plays a major role in the initiation and progression of breast cancer and our ultimate goal is to determine if environmentally induced gene repression plays a role as a trigger for the silencing events. The purpose of the proposed work was to confirm or refute the hypothesis. The anticipated scope of the work was to test tumor suppressor promoters known to silence in breast cancer for repression-mediated gene silencing, but we soon realized that this scope was too ambitious for a one-year funding period. We therefore changed the scope somewhat to ensure that during the funding period we could at least test the basic principle of the hypothesis. This approach was successful and we have now demonstrated that gene repression can induce gene silencing in mammalian cells. Moreover, we have recently acquired functional tumor suppressor gene promoters that are silenced in breast cancer and can use remaining funds to test these promoters for repression-induced silencing.