title: Epidermal growth factor enhances the malignant phenotype in canine mammary carcinoma cell lines.
abstract: Canine mammary gland tumours (CMTs) are the most common malignancies in female dogs. The receptor tyrosine kinase EGFR (erbb1), a receptor for epidermal growth factor (EGF) and related factors, mediates multiple oncogenic functions in human epithelial neoplasms. While previous studies have demonstrated EGFR expression in canine tumours, its function has not been studied in canine cancer. The purpose of this study was to determine the in vitro effects of EGF and vandetanib (ZD6474), a small molecule inhibitor of VEGFR-2, EGFR and RET tyrosine kinases, on proliferation, invasion, survival and chemosensitivity in CMT cells. In low serum, EGF enhanced proliferation and chemotaxis, attenuated apoptosis, and stimulated vascular endothelial growth factor (VEGF) production. Vandetanib dose-dependently inhibited EGFR phosphorylation as well as PI3K/Akt activation, and inhibited all EGF-induced phenotypic effects. In conclusion, EGF stimulates multiple features promoting the malignant phenotype in CMT. Thus, CMT may be an important translational model for the investigation of novel EGFR-directed therapies.
authors.affiliation: The Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Kennedy
authors.forename: B A
authors.initials: BA
authors.lastname: Qurollo
authors.forename: B J
authors.initials: BJ
authors.lastname: Rose
authors.forename: D H
authors.initials: DH
authors.lastname: Thamm
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051096:Proto-Oncogene Proteins c-ret; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; C452423:vandetanib