title: Expression and mutational analysis of c-CBL and its relationship to the MET receptor in head and neck squamous cell carcinoma.
abstract: MET is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and degraded by c-CBL E3-ubiquitin ligase. We investigated genetic variations of c-CBL in HNSCC and the relationship between c-CBL and MET expression. High MET, low c-CBL expression was detected in 10 cell lines and 73 tumor tissues. Two novel mutations (L254S, L281F), and the single nucleotide polymorphism (SNP) P782L were identified from archival tumor tissues. 27.3% of loss of heterozygosity was found at CBL locus. Ectopic expression of wild-type c-CBL in SCC-35 cells downregulated MET expression and decreased cell viability. These results suggest MET overexpression is related to altered c-CBL expression, which may influence tumorigenesis.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Cleo E
authors.initials: CE
authors.lastname: Rolle
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Yi-Hung Carol
authors.initials: YC
authors.lastname: Tan
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Tanguy Y
authors.initials: TY
authors.lastname: Seiwert
authors.affiliation: Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
authors.forename: Sapana
authors.initials: S
authors.lastname: Vora
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Rajani
authors.initials: R
authors.lastname: Kanteti
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Rifat
authors.initials: R
authors.lastname: Hasina
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: George B
authors.initials: GB
authors.lastname: Carey
authors.affiliation: Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Mosmi
authors.initials: M
authors.lastname: Surati
authors.affiliation: Department of Radiation and Cellular Oncology/Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.affiliation: Department of Medical Oncology and Therapeutic Research, City of Hope, Duarte, CA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis
chemical_list: D050721:Proto-Oncogene Proteins c-cbl; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C067419:CBL protein, human
keywords: MET; c-CBL; head and neck cancer