Hypoxia-inducible factor-1alpha polymorphisms associated with enhanced transactivation capacity, implying clinical significance.
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.
Tanimoto
Keiji
K
Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
Yoshiga
Koji
K
Eguchi
Hidetaka
H
Kaneyasu
Mika
M
Ukon
Kei
K
Kumazaki
Tsutomu
T
Oue
Naohide
N
Yasui
Wataru
W
Imai
Kazue
K
Nakachi
Kei
K
Poellinger
Lorenz
L
Nishiyama
Masahiko
M
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
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