HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells.
Head Neck
; 36(11): 1547-54, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-24123531
ABSTRACT
BACKGROUND:
The purpose of this study was to identify mechanisms of innate resistance to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Specifically, we analyzed the role of HRAS mutations in erlotinib resistance.METHODS:
Erlotinib sensitivity was determined by methyl thiazolyl-tetrazolium (MTT) assays. Molecular signaling pathways and somatic mutations were examined. Changes in sensitivity after modulation of HRAS expression were evaluated.RESULTS:
All 7 cell lines were wild-type for EGFR and KRAS regardless of erlotinib sensitivity; however, 1 erlotinib-resistant cell line (HN31) harbored an HRAS G12D mutation. Downregulation of HRAS expression by small interfering RNA (siRNA) or short hairpin RNA (shRNA) in HN31 led to increased erlotinib sensitivity in vitro and in vivo. Transfection of activating HRAS-mutant (G12D and G12V) constructs into erlotinib-sensitive cell lines made them more resistant to erlotinib.CONCLUSION:
Activating HRAS mutations can confer erlotinib resistance in an HRAS mutant HNSCC cell line.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Quinazolinas
/
Proteínas Proto-Oncogénicas p21(ras)
/
Resistencia a Antineoplásicos
/
Terapia Molecular Dirigida
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Head Neck
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article