title: Oncological implications of hypoxia inducible factor-1alpha (HIF-1alpha) expression.
abstract: Solid tumours contain regions of hypoxia, which may be a prognostic indicator and determinant of malignant progression, metastatic development and chemoradio-resistance. The degree of intra-tumoural hypoxia has been shown to be positively correlated with the expression of the transcription factor hypoxia-inducible factor 1. HIF-1 is composed of 2 sub-units, namely HIF-1alpha and HIF-1beta. The production of hypoxia inducible factor 1-alpha has been identified as a key element in allowing cells to adapt and survive in a hostile hypoxic environment via a variety of pathways. HIF-1alpha is stabilised by hypoxia at the protein level, and also by the oncogenes HER2neu, v-src and ras. There are over 60 target genes for HIF-1, many of which are activated in cancers in comparison to equivalent normal tissues. Chemotherapeutic modulation of HIF-1 pathways has shown promise for patients with chemo-radio resistant or recurrent tumours in Phase II clinical trials. We herein review the existing literature on hypoxia inducible factor-1alpha, particularly its role in carcinogenesis and clinical implications of its over-expression.
authors.affiliation: RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
authors.forename: Jill L
authors.initials: JL
authors.lastname: O'Donnell
authors.forename: Myles R
authors.initials: MR
authors.lastname: Joyce
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Shannon
authors.forename: Judith
authors.initials: J
authors.lastname: Harmey
authors.forename: James
authors.initials: J
authors.lastname: Geraghty
authors.forename: David
authors.initials: D
authors.lastname: Bouchier-Hayes
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002986:Clinical Trials as Topic; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D051793:Hypoxia-Inducible Factor 1