title: Hypoxia-inducible factor-1alpha polymorphisms associated with enhanced transactivation capacity, implying clinical significance.
abstract: Hypoxia-inducible factor-1 (HIF-1) is a pivotal factor that regulates cellular responses to hypoxia and is presumably linked to regulation of angiogenesis and tumor growth. We assessed the difference in transcription activity of two HIF-1alpha polymorphic variants (P582S and A588T), along with molecular epidemiological study among head and neck squamous cell carcinoma (HNSCC) patients. Both HIF-1alpha variants revealed significantly higher transcription activity than wild-type (WT) did, under normoxic and hypoxic conditions (P < 0.02). Furthermore, tumors from HNSCC patients with heterozygous alleles having P582S or A588T had significantly increased numbers of microvessels compared with those with homozygous WT (P = 0.02). In addition, all patients with tumors of T1 (below 2 cm diameter) were WT, while 14 of 47 patients with tumors of > or =T2 were heterozygous. The elevated transactivation capacity of variant forms of HIF-1alpha implies a role of HIF-1alpha polymorphisms in generating individually different tumor progression.
authors.affiliation: Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshiga
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Eguchi
authors.forename: Mika
authors.initials: M
authors.lastname: Kaneyasu
authors.forename: Kei
authors.initials: K
authors.lastname: Ukon
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kumazaki
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
authors.forename: Kazue
authors.initials: K
authors.lastname: Imai
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Lorenz
authors.initials: L
authors.lastname: Poellinger
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishiyama
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D011110:Polymorphism, Genetic; D014157:Transcription Factors; D015533:Transcriptional Activation
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors