Journal Article

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

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

in Carcinogenesis

Volume 24, issue 11, pages 1779-1783
Published in print November 2003 | ISSN: 0143-3334
Published online November 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg132
Hypoxia-inducible factor-1α polymorphisms associated with enhanced transactivation capacity, implying clinical significance

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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-1α polymorphic variants (P582S and A588T), along with molecular epidemiological study among head and neck squamous cell carcinoma (HNSCC) patients. Both HIF-1α 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 ≥T2 were heterozygous. The elevated transactivation capacity of variant forms of HIF-1α implies a role of HIF-1α polymorphisms in generating individually different tumor progression.

Keywords: HIF-1, hypoxia-inducible factor-1; HNSCC, head and neck squamous cell carcinoma; N-TAD, N-terminal transactivation domain; pVHL, von Hippel-Lindau tumor suppressor protein; VEGF, vascular endothelial growth factor; WT, wild-type

Journal Article.  3453 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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