title: Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro.
abstract: Members of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro. Here we report that EGFR and ERBB2 combined siRNA targeting produced synergistic effects in feline and canine cell lines similar to that reported in human cell lines. We conclude that dual EGFR and ERBB2 targeting using TKIs should be further evaluated as a potential new therapeutic strategy in feline head and neck and mammary tumours and canine mammary tumours.
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Gray
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: McDowell
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: M
authors.initials: M
authors.lastname: Erskine
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: Q T M
authors.initials: QTM
authors.lastname: Loh
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: O
authors.initials: O
authors.lastname: Grice
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Argyle
authors.affiliation: The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: G T
authors.initials: GT
authors.lastname: Bergkvist
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002371:Cat Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002415:Cats; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D004357:Drug Synergism; D066246:ErbB Receptors / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D066298:In Vitro Techniques; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: cell signalling; comparative oncology; gene therapy; in vitro models; small animal; tumour biology; tyrosine kinase