Immortalized breast epithelial cell lines from normal breast with luminal and intrinsic subtypes – enriched gene expression

The cell-type origin has long been suspected to determine molecular features of tumors but has proven difficult to experimentally validate in human breast cancers because of deficiencies in culturing methods that allow propagation of three major cell types of the breast including stem/basal, luminal-progenitor and mature/differentiated cells. We have created immortalized cell lines from core breast biopsies of ancestry-mapped healthy women that are enriched for luminal gene expression including hormonally sensitive ERa-FOXA1-GATA3 transcription factor network. Gene expression pattern followed by intrinsic subtype classification identified these cell lines as “normal” counterpart to luminal A, basal, and normal-like subtypes of breast cancers. We have also created cell lines from CD201+/EpCAM- cells that are likely “normal” counter part of claudin-low subtype of breast cancers. These cell lines serve as good resources as “normal” cell line controls for breast cancer-related studies. Overall design: We propagated breast epithelial cells from breast core biopsies of healthy women using the epithelial reprogramming assay (Nakshatri et al., Scientific Reports, 5:13526). Primary cells were immortalized using human telomerase (hTERT). RNA from immortalized cells in triplicates was subjected to RNA-seq and results are included. hTERT immortalized HME cells from Horizon Discovery, MCF10A cells from ATCC and MCF7 breast cancer cells from ATCC were used as controls for comparison. 1505-10B corresponds to immortalized cells with germ line BRCA2 mutation. KTB40 and KTB42 differ from the rest of the cell lines with respect to cell surface markers profiles. These cells are CD201+/EpCAM-, whereas the remaining cells are CD201+/EpCAM+ or CD201-/EpCAM+. KTB40 and KTB42 are phenotypically fibroblastic or display features of epithelial to mesenchymal transition, whereas the remaining KTB (Komen Tissue Bank) cell lines display luminal features. This series also includes RNA-seq data for non-immortalized cell lines.

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Kumar B, Prasad M, Bhat-Nakshatri P, Anjanappa M, Kalra M, Marino N, Storniolo AM, Rao X, Liu S, Wan J, Liu Y, Nakshatri H