| http://purl.uniprot.org/citations/21765473 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21765473 | http://www.w3.org/2000/01/rdf-schema#comment | "BRCA1 mutation-associated breast cancer originates in oestrogen receptor-alpha-negative (ER(-)) progenitors in the mammary luminal epithelium. These cells also express high levels of the Kit gene and a recent study demonstrated a correlation between Brca1 loss and Kit over-expression in the mammary epithelium. However, the functional significance of c-Kit expression in the mammary gland is unknown. To address this, c-Kit(-) and c-Kit(+) mammary epithelial subsets were isolated by flow cytometry, characterised for expression of lineage-specific cell markers and functionally analysed by in vitro colony forming and in vivo transplantation assays. The results confirm that the majority of luminal ER(-) progenitors are c-Kit(+), but also that most stem cells and the differentiated cell populations are c-Kit(-). A subset of c-Kit(+) cells with high proliferative potential was found in the luminal ER(+) population, however, suggesting the existence of a distinct luminal ER(+) progenitor cell type. Analysis of mouse Brca1 mammary tumours demonstrated that they expressed Kit and its downstream effector Lyn at levels comparable to the most strongly c-Kit(+) luminal ER(-) progenitors. Consistent with c-Kit being a progenitor cell marker, in vitro three-dimensional differentiation of c-Kit(+) cells resulted in a loss of c-Kit expression, whereas c-Kit over-expression prevented normal differentiation in vivo. Furthermore, c-Kit was a functional marker of proliferative potential, as c-Kit inhibition by short hairpin knockdown prevented normal epithelial growth and caused cells to undergo apoptosis. Therefore, c-Kit defines distinct progenitor populations in the mammary epithelium and is critical for mammary progenitor survival and proliferation. Importantly, c-Kit is only the second mammary epithelial stem/progenitor marker to be shown to have a functional role in the mammary epithelium and the first marker to be shown to be required for progenitor cell function. The c-Kit signalling network has potential as a target for therapy and/or prevention in BRCA1-associated breast cancer."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2011.289"xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/author | "Groner B."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/author | "Kendrick H."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/author | "Smalley M.J."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/author | "Regan J.L."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/author | "Vafaizadeh V."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/author | "Magnay F.A."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/pages | "869-883"xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/title | "c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer."xsd:string |
| http://purl.uniprot.org/citations/21765473 | http://purl.uniprot.org/core/volume | "31"xsd:string |
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