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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 Res

Publication Date

01/10/2003

Volume

63

Pages

6130 - 6134

Keywords

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