Role of Epithelial-Mesenchymal Transition in the Formation of Normal and Neoplastic Mammary Epithelial Stem Cells

摘要

The epithelial-mesenchymal transition (EMT) has been found by us and others to induce normal and neoplastic mammary epithelial cells (MECs) to acquire mesenchymal traits and, in addition, many of the characteristics of stem cells. However, none of these observations showed that the products of EMT are actually bona fide stem cells. To demonstrate this, I had optimized efficient EMT induction in several different cell types, tested new ways of separating stem cell and non-stem cell populations of normal and breast cancer cells and identified EMT transcription factors most likely involved in stem cell biology. Preliminary results directly demonstrate that transient induction of EMT increases the number of mammary epithelial stem cells capable of generating an entire mammary ductal tree. With these observations and optimizations I can now move closer to uncovering the connection between EMT and entrance into a stem-cell state. The outcome of these experiments holds important implications for the mechanisms controlling the formation of normal mammary epithelial stem cells as well as the formation of breast cancer stem cells.