title: Overexpression of ErbB2 impairs ligand-dependent downregulation of epidermal growth factor receptors via a post-transcriptional mechanism.
abstract: The mechanism by which ErbB2 exerts its oncogenic effect is poorly defined. In this article we show that ErbB2 co-expression slows ligand-dependent growth factor receptor downregulation in NIH 3T3 transfectants. Ligand dependence of cell growth and MAP kinase signaling are retained in epidermal growth factor receptor (EGFR) transfectants but are abolished in ErbB2-expressing cells, which grow and signal constitutively. In association with this phenomenon, we have noticed that ErbB2-expressing cells contain increased amounts of EGFR, which is hyperphosphorylated. EGFR overexpressors do not contain increased levels of ErbB2, however, tending to exclude a transfection artifact caused by saturation of receptor processing. EGF treatment of EGFR transfectants results in more rapid EGFR downregulation than occurs in ErbB2 transfectants, but Northern blot analysis demonstrates reduced basal EGFR gene expression in ErbB2 transfectants. We conclude that ErbB2 expression impairs EGFR downregulation via a posttranscriptional mechanism and propose that ErbB2 overexpression may sensitize tumor cells to the mitogenic effects of heterologous growth factors by retarding degradation of liganded heterodimers.
authors.affiliation: Department of Medicine, King's College School of Medicine, London, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.forename: A
authors.initials: A
authors.lastname: Chantry
authors.forename: R J
authors.initials: RJ
authors.lastname: Epstein
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D010766:Phosphorylation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D066246:ErbB Receptors; D008024:Ligands; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases