Abstract
IntroductionMammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized. Breast tumors can be divided into subgroups, each one requiring specific treatment. To determine a possible association between mammary stem cells and breast cancer, a detailed characterization of the transcriptome in mammary stem cells is essential.MethodsWe have used a 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 have performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype-specific and prognosis gene signatures, and correlated gene expression to in vivo mammary gland development.ResultsOur analysis of mammary stem-like and stepwise cell differentiation, and an in-depth description of our findings in a breast cancer perspective provide a unique map of the transcriptomic changes and a number of novel mammary stem cell markers. We correlate the alterations to in vivo mammary gland differentiation, and describe novel changes in nuclear receptor gene expression. Interestingly, our comparisons show that specific subtypes of breast cancers with poor prognosis and metastasizing capabilities show resemblance to stem-like gene expression.ConclusionsThe transcriptional characterization of these mammary stem-like cells and their differentiation-induced gene expression patterns is here made widely accessible and provides a basis for research on mammary stem-like cells. Our comparisons suggest that some tumors are more stem-like than others, with a corresponding worse prognosis. This information would, if established, be important for treatment decisions. We also suggest several marker candidates valuable to investigate further.
Highlights
Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized
Our comparisons show that specific subtypes of breast cancers with poor prognosis and metastasizing capabilities show resemblance to stem-like gene expression
Our analysis confirmed previous findings, including: an increase of Stat1 and Stat5a during differentiation, which mimics the in vivo control of proliferation, differentiation and survival during mammary gland differentiation [18]; an increase of Ctgf expressed, found in the in vivo mouse mammary gland during pregnancy and lactation [19]; an increase of Lamp1, a differentiation marker for HC11 [20]; and an increase of Igfbp5, whose expression is stimulated during cellular differentiation by lactogenic hormones [21]
Summary
Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized. For each round of pregnancy, the mammary gland undergoes sequential cycles of proliferation, differentiation and apoptosis, and alveolar ducts form and grow, differentiate to produce milk and, after lactation, cease, revert and regress to the pre-pregnancy state. These and several other observations point towards the presence of stem cells as the basis for the capacity for alveolar renewal in each pregnancy (reviewed in [1]). A bipotential mammary epithelial stem cell and/or a luminal progenitor cell would, via acquired genetic alterations, epigenetic changes and para-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
