title: Mutational analysis of Noxa gene in human cancers.
abstract: There has been mounting evidence that dysregulation of apoptosis is involved in the mechanisms of cancer development and somatic mutations of apoptosis-related genes have been reported in human cancers. Noxa, a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family, is known to interact with anti-apoptotic Bcl-2 family members and induces apoptosis. The aim of this study was to explore the possibility that the Noxa gene is mutated in human cancers. We have analyzed the entire coding region and all splice sites of the Noxa gene for the detection of somatic mutations in a series of human cancers, including carcinomas from stomach, colon, liver, urinary bladder and lung by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing. We found one somatic mutation of the Noxa gene in a transitional cell carcinoma (TCC) of the urinary bladder. To evaluate the functional alterations of the mutant in apoptosis, we overexpressed the mutant and wild-type Noxa in 293T and HeLa cells, but could not find any significant difference in cell death between the wild-type and mutant Noxa. These data suggest that Noxa is rarely mutated in human carcinomas and that the contribution of Noxa gene mutation in the pathogenesis of human cancer might not be related to cell death mechanisms.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Soung
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Jong Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Jong Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jik Young
authors.initials: JY
authors.lastname: Park
authors.forename: Yong Gu
authors.initials: YG
authors.lastname: Cho
authors.forename: Chang Jae
authors.initials: CJ
authors.lastname: Kim
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2