Implications of Stem Cell Growth Regulation for Breast Cancer

Abstract : We propose that mammary stem cells could be involved in tumor development in either of two ways. The first is that altered function could change the course of development, and affect the susceptibility to transformation in adult life. We have found and characterized a model to test this hypothesis, and have preliminary array data to describe these cell populations. The second way that mammary stem cells could affect tumor development is by direct recruitment of these cells as tumor precursors. We have characterized a model of carcinogen-induced tumor development, and show that canonical stem cells are highly sensitive to genotoxins, and unlikely to be direct precursor cells. In order to study the factors that regulate mammary epithelial cell growth, we have chosen to examine their interaction in microchannels. These are very small-scale culture devices that allow for the culture of cells in defined media in low volumes. We have found that mammary stem/progenitor cells induce the division of the cell majority, suggesting an entirely novel function for this group of cells.