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Tumor hypoxia induces the up-regulation of a gene program associated with angiogenesis, glycolysis, adaptation to pH, and apoptosis via the hypoxia-inducible transcription factors (Hifs) 1 and 2. Disruption of this pathway has been proposed as a cancer therapy. Here, we use short interfering RNAs to compare specific inactivation of Hif-1alpha or Hif-2alpha and show markedly different cell type-specific effects on gene expression and cell migration. Remarkably, among a panel of hypoxia-inducible genes, responses were critically dependent on Hif-1 alpha but not Hif-2 alpha in both endothelial and breast cancer cells but critically dependent on Hif-2 alpha in renal carcinoma cells.

Type

Journal article

Journal

Cancer research

Publication Date

10/2003

Volume

63

Pages

6130 - 6134

Addresses

Cancer Research UK, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.

Keywords

Endothelium, Vascular, Cell Line, Tumor, Humans, Carcinoma, Renal Cell, Breast Neoplasms, Kidney Neoplasms, Trans-Activators, Transcription Factors, RNA, Small Interfering, Transfection, Cell Movement, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Basic Helix-Loop-Helix Transcription Factors, Hypoxia-Inducible Factor 1, alpha Subunit, Transcriptional Activation