title: GPx3 promoter hypermethylation is a frequent event in human cancer and is associated with tumorigenesis and chemotherapy response.
abstract: Glutathione peroxidase 3 (GPx3), a plasma antioxidant enzyme, maintains genomic integrity by inactivating reactive oxygen species (ROS), known DNA-damaging agents and mediators of cancer chemotherapy response. In this study, we demonstrate that loss of GPx3 expression by promoter hypermethylation is frequently observed in a wide spectrum of human malignancies. Furthermore, GPx3 methylation correlates with head and neck cancer (HNC) chemoresistance and may serve as a potential prognostic indicator for HNC patients treated with cisplatin-based chemotherapy. Our findings support the hypothesis that defects in the antioxidant system may contribute to tumorigenesis of a wide spectrum of human malignancies. GPx3 methylation may have implications in chemotherapy response and clinical outcome of HNC patients.
authors.affiliation: Medical Sciences Program, Indiana University School of Medicine, 1001 E. Third St., Bloomington, IN, USA.
authors.forename: Baishen
authors.initials: B
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Rao
authors.forename: Michael G
authors.initials: MG
authors.lastname: House
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Cullen
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase