Abstract
Abstract To understand relationships between breast tissue, 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 defined subpopulations that are highly enriched for mammary stem, luminal progenitor and mature luminal cells. Transcriptome analyses of mouse and human mammary epithelial populations has led to the identification of multiple conserved genes and pathways. 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. The role of the zinc finger transcription factor Gata-3, a critical regulator of luminal cell differentiation and a favourable prognostic indicator in breast cancer, has recently been explored in tumor initiation using mouse models. Gata-3 deficiency was found to increase the tumorigenicity of different epithelial subpopulations, with accompanying cell-fate changes. In the context of human breast tissue, analogous studies have enabled us to pinpoint the cellular defect occurring in precancerous tissue from BRCA1 mutation carriers. These carriers were shown to harbor aberrant luminal progenitor cells. Combined with interrogation of the molecular profiles of the different subtypes of breast cancer, the luminal progenitor was identified as the likely cell of origin for BRCA1-associated basal cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY12-03. doi:10.1158/1538-7445.AM2011-SY12-03
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