title: The resistance of macrophage-like tumour cell lines to growth inhibition by lipopolysaccharide and pertussis toxin.
abstract: The process of tumorigenesis is frequently associated with resistance to growth inhibition by physiological regulators of normal cells. Murine macrophage-like cell lines BAC1.2F5, RAW264, J774.1A and PU5/1.8 were resistant to growth inhibition by bacterial lipopolysaccharide (LPS) and pertussis toxin, agents that blocked growth of primary bone marrow-derived macrophages (BMDM) in the presence of macrophage colony-stimulating factor (CSF-1). The resistance of the CSF-1-dependent cell line BAC1.2F5 to growth inhibition by pertussis toxin argues against the possibility that pertussis toxin-sensitive G proteins are essential for the pathway of growth stimulation by CSF-1. Conversely, these data add further weight to the argument that LPS mediates some of its biological activities by mimicking the action of pertussis toxin and inhibiting G protein function. The resistance of cell lines to LPS and pertussis toxin was not correlated with any alteration in the expression of mRNA encoding any of three pertussis-toxin sensitive G protein alpha subunits. The pattern of G protein expression was consistent between primary cells and tumour cells, suggesting that this is a differentiation marker. In particular, Gi alpha 2 mRNA was expressed at remarkably high levels in all of the cells. The specificity of LPS resistance was investigated by studying down-regulation of CSF-1 binding and induction of protooncogene c-fos and tumour necrosis factor (TNF) mRNA. BAC1.2F5 cells were LPS-resistant in each of these assays. In CSF-1 binding, RAW264 and J774.1A responded in the same way as bone marrow-derived macrophages but required higher doses of LPS, whereas c-fos and TNF mRNA were induced in these cells at concentrations that did not inhibit growth. In PU5/1.8 cells, CSF-1 binding was already very low and was not further down-regulated, but c-fos and TNF mRNA was inducible by LPS. By contrast to primary macrophages, the cell lines did not respond to LPS with down-regulation of c-fms mRNA, which encodes the CSF-1 receptor. Hence, the resistance of macrophage-like tumour cells to LPS and pertussis toxin was specific to the pathways controlling growth, and was correlated with altered regulation of the CSF-1 receptor.
authors.affiliation: Centre for Molecular Biology and Biotechnology, University of Queensland, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: von Gavel
authors.forename: A I
authors.initials: AI
authors.lastname: Cassady
authors.forename: K J
authors.initials: KJ
authors.lastname: Stacey
authors.forename: T L
authors.initials: TL
authors.lastname: Dunn
authors.forename: D A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000187:drug effects; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D006131:Growth Inhibitors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D016173:Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin; D016186:Receptor, Macrophage Colony-Stimulating Factor; D019204:GTP-Binding Proteins