Skip to Content
Merck
  • HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells.

HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells.

Head & neck (2013-10-15)
J Hun Hah, Mei Zhao, Curtis R Pickering, Mitchell J Frederick, Genevieve A Andrews, Samar A Jasser, David R Fooshee, Zvonimir L Milas, Chad Galer, Daisuke Sano, William N William, Edward Kim, John Heymach, Lauren A Byers, Vali Papadimitrakopoulou, Jeffrey N Myers
ABSTRACT

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. 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. 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. Activating HRAS mutations can confer erlotinib resistance in an HRAS mutant HNSCC cell line.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human HRAS
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Pricing and availability is not currently available.
Supelco
Dimethyl sulfoxide, analytical standard
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%
Pricing and availability is not currently available.
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Pricing and availability is not currently available.
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Pricing and availability is not currently available.
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
Pricing and availability is not currently available.
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Pricing and availability is not currently available.
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Hras1
Pricing and availability is not currently available.