Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma.

ABSTRACT:

Purpose

Mitochondrial mutations have been identified in head and neck squamous cell carcinoma (HNSCC), but the pathways by which phenotypic effects of these mutations are exerted remain unclear. Previously, we found that mitochondrial ND2 mutations in primary HNSCC increased reactive oxygen species (ROS) and conferred an aerobic, glycolytic phenotype with HIF1alpha accumulation and increased cell growth. The purpose of the present study was to examine the pathways relating these alterations.

Experimental design

Mitochondrial mutant and wild-type ND2 constructs were transfected into oral keratinocyte immortal cell line OKF6 and head and neck cancer cell line JHU-O19 and established transfectants. The protein levels of HIF1alpha, pyruvate dehydrogenease (PDH), phosphorylated P

SUBMITTER: Sun W 

PROVIDER: S-EPMC2729126 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature