Abstract

Abstract Mammary stem cells are suggested to be the origin of breast cancer, but are elusive and vaguely characterized. Cancer may be sustained by cancer stem cells, that are resistant to common treatments like irradiation and chemotherapy. To determine a possible association between mammary stem cells and breast cancer, we have previously made a detailed characterization of the transcriptome in murine mammary epithelial stem-like cell line (HC11) and made a thorough investigation of global gene-expression changes during stepwise differentiation using dual-color comparative microarray technique. Subsequently, we performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype-specific and prognosis gene signatures. Our analysis provided a unique map of the transcriptomic changes and a number of novel mammary stem cell markers. Our comparisons showed a relationship between breast cancers of poor prognosis and stem-like gene expression. In particular the specific subtypes of basal like tumors and Luminal C types, which both have a poor prognosis, showed stem cell like gene expression pattern. We are subsequently investigating regulations of miRNAs during differentiation. We have found very strong miRNA regulation during differentation of the stem cell like cells, and are investigating the functions of key regulated miRNAs. We imply the same miRNAs could be affecting poor prognosis breast cancers. By defining the association between mammary stem cell like cells and stem cell like tumors, we can start to understand the pathways that will need to be targeted for successful treatment of poor prognosis breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2076.

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