Expression and mutational analysis of c-CBL and its relationship to the MET receptor in head and neck squamous cell carcinoma
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Cleo E. Rolle1,*, Yi-Hung Carol Tan1,*, Tanguy Y. Seiwert1, Sapana Vora2, Rajani Kanteti1, Rifat Hasina1, George B. Carey1, Mosmi Surati3, Ralph R. Weichselbaum4, Mark W. Lingen5, Everett E. Vokes1, Ravi Salgia6
1Department of Medicine, The University of Chicago, Chicago, IL, USA
2Department of Pediatrics, The University of Chicago, Chicago, IL, USA
3Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA
4Department of Radiation and Cellular Oncology/Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA
5Department of Pathology, The University of Chicago, Chicago, IL, USA
6Department of Medical Oncology and Therapeutic Research, City of Hope, Duarte, CA, USA
*These authors have contributed equally to this work
Ravi Salgia, email: [email protected]
Keywords: c-CBL, MET, head and neck cancer
Received: October 01, 2015 Accepted: April 16, 2016 Published: May 26, 2016
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.
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