Gene expression profiling of breast cell lines identifies potential new basal markers

Abstract

International audienceA better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression pro. ling 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

MYC-induced apoptosis in mammary epithelial cells is associated with repression of lineage-specific gene signatures

“…1A). [23][24][25] To validate repression of basal marker genes by MYC, we isolated RNA from pools of MYC-ER and MYCVD-ER MCF10A cells after 24 hours of 4-OHT treatment and tested expression of 3 genes: KRT14, LAMC2 and ITGA6. We observed an approximately 50 % reduction of relative mRNA expression for all 3 genes upon activation of MYC-ER (Fig.…”

The Forkhead Box Transcription Factor FOXC1 Promotes Breast Cancer Invasion by Inducing Matrix Metalloprotease 7 (MMP7) Expression

“…Interestingly, the cell lines with the greatest FOXC1 and MMP7 expression were basal A breast cancer lines (27). These cell lines have gene expression patterns that most closely correlate with BLBC (27,28). Hence, basal A breast cancer cell lines such as HCC1187 may serve as superior models than basal B lines such as MDA-MB-231 for understanding BLBC and the roles of FOXC1 and MMP7 in this disease.…”

“…2D). Notably, the breast cancer cell lines that exhib-ited the highest expression of FOXC1 and MMP7 are those classified as basal A, whereas luminal and basal B/mesenchymal-like breast cancer cells lines showed low or moderate expression of FOXC1 and MMP7 (27,28). Basal A cell lines are most like BLBC, whereas basal B lines are more similar to the rare claudin-low breast cancer subtype.…”

Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes

“…Using whole-genome DNA microarrays and immunohistochemistry (IHC), we have recently established gene and protein expression profiles of 31 breast cell lines (BCLs) and generated a 10-protein signature (CAV1,CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and Moesin) allowing accurate distinction between luminal and basal BCLs (8).…”