Functional culture models to study mechanisms governing apoptosis in normal and malignant mammary epithelial cells.

Mammary tissue homeostasis depends upon dynamic interactions between the epithelial cells, their microenvironment (including the basement membrane and the stroma), and the tissue architecture, which influence each other reciprocally to regulate growth, death and differentiation in the gland. To study how apoptosis is regulated in normal mammary cells, and to understand its role in breast tumor pathogenesis, we need model systems that recapitulate breast tissue architecture and microenvironment in culture. We have established culture models of primary and established nonmalignant mammary cell lines from both rodent and human, and defined procedures to study how cell and tissue architecture affect signaling by the basement membrane. We show that both a basement membrane and an organized tissue structure are required to achieve sustained mammary cell survival. These models could now be used to investigate how the basement membrane represses apoptosis in normal cells, and how breast cancers become death-resistant.