Oncological implications of hypoxia inducible factor-1alpha (HIF-1alpha) expression.
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.
O'Donnell
Jill L
JL
RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Joyce
Myles R
MR
Shannon
Aoife M
AM
Harmey
Judith
J
Geraghty
James
J
Bouchier-Hayes
David
D
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
D014408:Biomarkers, Tumor; D051793:Hypoxia-Inducible Factor 1