Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse Mammary Epithelium

摘要

Develop an immunohistochemical method for identifying stem cells and stem cell niches, and to use this to determine if in utero estrogenic overstimulation causes changes in the number of stem cells or their niches. To extend the power of ex vivo stem cell isolation and enumeration by providing a way to identify functional cell types in situ. This identification method should ultimately provide a diagnostic refinement for mammary cancers. We had marginal success due primarily to (1) most antibodies previously reputed to be stem cell specific turned out to be present in differentiated mammary cell types as well as putative progenitor cells; (2) some of these antibodies stained all cell types but not all members of each subset; (3) technical limitations: our inability to detect 2 to 3 antibodies simultaneously with hematoxylin counterstain. Due to these events, as with ex vivo characterization, we were unable to discover definitive markers for any cell type, however we did show that P63, originally thought to be a stem cell marker, but shown later to be an epithelial stratification organizer, is expressed differentially in the basal and luminal cells depending on the stage of estrus cycle, and whether the tissue is tumorigenic. Due to the technical challenges the main animal study was not realized.