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Hypoxia-inducible factor-1 polymorphisms associated with enhanced transactivation capacity, implying clinical significance

2003; Oxford University Press; Volume: 24; Issue: 11 Linguagem: Inglês

10.1093/carcin/bgg132

1460-2180

Keiji Tanimoto, Koji YOSHIGA, Hidetaka Eguchi, Mika Kaneyasu, Kei Ukon, Tsutomu Kumazaki, Naohide Oue, Wataru Yasui, Kazue Imai, Kei Nakachi, Lorenz Poellinger, Masahiko Nishiyama,

High Altitude and Hypoxia

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.