Abstract

Abstract To understand relationships between the mammary epithelia, ‘cells of origin’ and cancer stem cells in breast tumors, it is necessary to dissect the normal mammary epithelial hierarchy. We have isolated discrete populations of mouse and human mammary epithelial cells on the basis of cell-surface markers and identified cell subsets that are highly enriched for mammary stem (MaSC), luminal progenitor and mature luminal cells. Analysis of different mouse models of mammary tumorigenesis using syngeneic transplantation assays and interrogation of molecular profiles has revealed potential ‘cells of origin’ in preneoplastic tissue and the presence of a definitive cancer stem cell subset in different mouse mammary tumors. Cell lineage tracing studies in the mouse provide the current gold standard for identifying cells of origin. Towards this end, we have constructed a series of transgenic mice harboring lineage-specific gene regulatory regions (180 kB) that can be used to direct the expression of specific mammary oncogenes to discrete epithelial cell types. This will allow us to address the contribution of ‘cells of origin’ and the nature of the oncogene itself to mouse mammary tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY10-04. doi:1538-7445.AM2012-SY10-04

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