Modulation of ATM gene expression in a murine mammary epithelial cell line

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To explore the role of atm in epithelial cell biology, we have used an in vitro model, in which non-transformed TAC-2 murine mammary epithelial cells recapitulate features of normal breast epithelium differentiation, when grown in a three-dimensional collagen gel. To modulate atm gene expression or impair atm function we designed antisense and dominant negative constructs which were delivered into TAC-2 cells through conventional plasmids. However, since these vectors failed to achieve effective long-term transgene expression, we have then used lentiviral vectors to express our constructs in TAC-2 cells with greater efficiency. We plan to use this model to assess the impact of atm dysfunction on the following parameters: cell proliferation and survival, cell cycle progression and morphogenetic properties. These investigations are expected to better delineate the contribution of the atm gene as a cancer-predisposing gene in the breast and to provide further insights into our understanding of atm function in epithelial cell biology.