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The role of the canonical NF-κB pathway in mammary tumorigenesis was investigated using a transgenic (TG) mouse expressing a dominant-negative inhibitor of κB (IκBαSR (S32A/S36A)) in the mammary gland under the control of the mouse mammary tumor virus promoter (MMTV). TG and control mice were subjected to a chemical carcinogenesis protocol. Hyperkeratinized squamous metaplasias (cytokeratin−6+/p63+) sometimes with a basaloid island component, were found in both TG and control mice whereas luminal (cytokeratin-19+/MUC1+) ErbB2+ papillary and adenomatous lesions developed almost exclusively in control mice. p65/RelA- and NF-κB DNA-binding activity were detected in mammary luminal lesions, but rarely in squamous metaplasias. Analysis of NF-κB family proteins and target genes using microarray data from a cohort of human mammary tumors revealed the expression of a canonical NF-κB pathway, but not non-canonical pathway proteins in HER2+ luminal cancers. HER2+ tumors also showed differential regulation of specific NF-κB target genes relative to basal and ER+ luminal cancers. Isolation of mammary cell populations enriched for stem and progenitor cell characteristics from an NF-κB-EGFP reporter mouse by fluorescence-activated cell sorting demonstrated that luminal progenitors contain activated NF-κB whereas the mammary stem cell-enriched population, does not. Together these data suggest that the canonical NF-κB pathway is active in normal luminal progenitor cells before transformation and is required for the formation of mammary luminal-type epithelial neoplasias.Oncogene (2009) 28, 2710–2722; doi:10.1038/onc.2009.131; published online 1 June 2009 [ABSTRACT FROM AUTHOR]

A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on ‘cell microarrays’ (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published ‘intrinsic 500-gene set’ assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management.Oncogene (2006) 25, 2273–2284. doi:10.1038/sj.onc.1209254; published online 14 November 2005 [ABSTRACT FROM AUTHOR]