title: Selection for EGFR gene amplification in a breast epithelial cell line with basal-like phenotype and hereditary background.
abstract: An epithelial cell line, referred to as A163, was established from breast carcinoma derived from a patient with a strong family history of breast cancer but no known breast cancer susceptibility mutation. A163 was propagated in a serum-free culture medium including the epidermal growth factor. Immunophenotypic characterization demonstrated a mixed luminal and basal-like phenotype. When epidermal growth factor was excluded from the culture medium, A163 entered a quiescent period followed by a period of increased cell proliferation in a subpopulation of the cells. The epidermal growth factor-independent subpopulation retained the basal-like phenotype of the parental cell line. Karyotype and fluorescent in situ hybridization analysis showed an amplification of epidermal growth factor receptor on 7q in A163-S1 only, resulting in high expression of total and phosphorylated epidermal growth factor receptor. The A163-S1 sub-line piles up in culture, indicating a loss of contact inhibition. When grown on transwell filters, A163 shows basal expression of P63 and cytokeratin 14, whereas A163-S1 expresses P63 ubiquitously, and has lost the basal specific expression of cytokeratin 14, indicating a loss of polarity. Furthermore, when cultured in reconstituted basement membrane matrix, A163 form polarized normal like acini. In contrast, A163-S1 form large disorganized structures with lack of polarity. These cell lines may prove useful to understand molecular changes in breast cancer progression, in particular basal-like breast cancer subtype with bad prognosis and no current treatment options.
authors.affiliation: Stem Cell Research Unit, Biomedical Center, University of Iceland and Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Saevar
authors.initials: S
authors.lastname: Ingthorsson
authors.forename: Thorhallur
authors.initials: T
authors.lastname: Halldorsson
authors.forename: Valgardur
authors.initials: V
authors.lastname: Sigurdsson
authors.forename: Agla J R
authors.initials: AJ
authors.lastname: Friðriksdottir
authors.forename: Sigridur K
authors.initials: SK
authors.lastname: Bodvarsdottir
authors.forename: Margret
authors.initials: M
authors.lastname: Steinarsdottir
authors.forename: Oskar
authors.initials: O
authors.lastname: Johannsson
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Magnusson
authors.forename: Helga M
authors.initials: HM
authors.lastname: Ogmundsdottir
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Gudjonsson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000473:pathology*; D012641:Selection, Genetic
chemical_list: D016895:Culture Media, Serum-Free; D004815:Epidermal Growth Factor; D066246:ErbB Receptors