title: Growth, differentiation and survival of HC11 mammary epithelial cells: diverse effects of receptor tyrosine kinase-activating peptide growth factors.
abstract: The HC11 mouse mammary epithelial cells are a useful in vitro model of mammary cell differentiation. When treated with the lactogenic hormones mix dexamethasone, insulin and prolactin (DIP) these cells synthesize the milk protein beta-casein. HC11 cells express receptor tyrosine kinases (RTK) of various subclasses. Here we present an analysis of the effect of their stimulation on growth, differentiation and survival. Growth conditions are an important part in the HC11 cell differentiation program. In order to respond optimally to DIP, cells must be grown to confluency in medium containing epidermal growth factor (EGF) plus insulin, at which stage the cells are defined as competent. During the growth phase all the peptide factors rested in this study: EGF, fibroblast growth factor (FGF)-2, insulin, IGF-I, platelet-derived growth factor (PDGF) and stem cell factor (SCF), stimulated MAP kinase (ERK2) activity and-DNA synthesis. However, not all factors were equivalent in promoting competency. Only FGF-2 replaced EGF during growth, while IGF-1 or SCF were able to substitute for insulin. PDGF replaced neither EGF nor insulin and was ineffective as a competence factor. The only peptide which could substitute for insulin in the lactogenic DIP mix and induce beta-casein synthesis was IGF-1, albeit at a high concentration. Competent cultures of HC11 cells maintained in serum-free medium in the presence of only dexamethasone and prolactin undergo apoptosis, which is prevented by the addition of either insulin, IGF-1, FGF-2, or EGF, but not PDGF or SCF. We conclude that in HC11 cells all peptide factors induce DNA synthesis but have distinct effects on differentiation and survival in HC11 cells.
authors.affiliation: Friedrich Miescher Institute, Basel/Switzerland.
authors.forename: G R
authors.initials: GR
authors.lastname: Merlo
authors.forename: D
authors.initials: D
authors.lastname: Graus-Porta
authors.forename: N
authors.initials: N
authors.lastname: Cella
authors.forename: B M
authors.initials: BM
authors.lastname: Marte
authors.forename: D
authors.initials: D
authors.lastname: Taverna
authors.forename: N E
authors.initials: NE
authors.lastname: Hynes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002364:Caseins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D008934:Mitogens / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000819:agonists* / Q000502:physiology
chemical_list: D002364:Caseins; D006133:Growth Substances; D008934:Mitogens; D004247:DNA; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1