title: Establishment of a normal-derived estrogen receptor-positive cell line comparable to the prevailing human breast cancer subtype.
abstract: Understanding human cancer increasingly relies on insight gained from subtype specific comparisons between malignant and non-malignant cells. The most frequent subtype in breast cancer is the luminal. By far the most frequently used model for luminal breast cancer is the iconic estrogen receptor-positive (ERpos) MCF7 cell line. However, luminal specific comparisons have suffered from the lack of a relevant non-malignant counterpart. Our previous work has shown that transforming growth factor-β receptor (TGFβR) inhibition suffices to propagate prospectively isolated ERpos human breast luminal cells from reduction mammoplasties (HBEC). Here we demonstrate that transduction of these cells with hTERT/shp16 renders them immortal while remaining true to the luminal lineage including expression of functional ER (iHBECERpos). Under identical culture conditions a major difference between MCF7 and normal-derived cells is the dependence of the latter on TGFβR inhibition for ER expression. In a breast fibroblast co-culture model we further show that whereas MCF7 proliferate concurrently with ER expression, iHBECERpos form correctly polarized acini, and segregate into proliferating and ER expressing cells. We propose that iHBECERpos may serve to shed light on hitherto unappreciated differences in ER regulation and function between normal breast and breast cancer.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Danish Stem Cell Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Branden M
authors.initials: BM
authors.lastname: Hopkinson
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Danish Stem Cell Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Klitgaard
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Danish Stem Cell Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Ole William
authors.initials: OW
authors.lastname: Petersen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Danish Stem Cell Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: René
authors.initials: R
authors.lastname: Villadsen
authors.affiliation: Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Rønnov-Jessen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Danish Stem Cell Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D060833:Cellular Microenvironment; D018920:Coculture Techniques; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D018125:Receptors, Transforming Growth Factor beta; D004958:Estradiol; C509186:TERT protein, human; D019098:Telomerase
keywords: breast cancer; estrogen receptor; human breast; immortalized luminal cells