title: Comparative analysis of MAPK and PI3K/AKT pathway activation and inhibition in human and canine melanoma.
abstract: The lack of advanced animal models of human cancers is considered a barrier to developing effective therapeutics. Canine and human melanomas are histologically disparate but show similar disease progression and response to therapies. The purpose of these studies was to compare human and canine melanoma tumours and cell lines regarding MAPK and PI3K/AKT signalling dysregulation, and response to select molecularly targeted agents. Pathway activation was investigated via microarray and mutational analysis. Growth inhibition and cell cycle effects were assessed for pathway inhibitors AZD6244 (MAPK) and rapamycin (PI3K/AKT) in human and canine melanoma cells. Human and canine melanoma share similar differential gene expression patterns within the MAPK and PI3K/AKT pathways. Constitutive pathway activation and similar sensitivity to AZD6244 and rapamycin was observed in human and canine cells. These results show that human and canine melanoma share activation and sensitivity to inhibition of cancer-related signalling pathways despite differences in activating mutations.
authors.affiliation: Cell and Molecular Biology Program, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.|Flint Animal Cancer Center, Veterinary Medical Center, Colorado State University, Fort Collins, CO, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Fowles
authors.affiliation: Flint Animal Cancer Center, Veterinary Medical Center, Colorado State University, Fort Collins, CO, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Denton
authors.affiliation: Cell and Molecular Biology Program, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.|Flint Animal Cancer Center, Veterinary Medical Center, Colorado State University, Fort Collins, CO, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Gustafson
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics; D004285:Dogs; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary; D008565:Membrane Proteins / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D009154:Mutation; D051058:Oncogene Protein v-akt / Q000378:metabolism; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D046888:Tissue Array Analysis
chemical_list: C517975:AZD 6244; D000903:Antibiotics, Antineoplastic; D001562:Benzimidazoles; D008565:Membrane Proteins; C482119:BRAF protein, human; D051058:Oncogene Protein v-akt; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D020123:Sirolimus
keywords: MAPK; PI3K/AKT pathway; canine; human; melanoma