Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Basic Helix-Loop-Helix Transcription Factors
-
Breast Neoplasms / genetics
-
Breast Neoplasms / metabolism
-
Breast Neoplasms / pathology
-
Carcinoma, Renal Cell / genetics
-
Carcinoma, Renal Cell / metabolism
-
Carcinoma, Renal Cell / pathology
-
Cell Hypoxia / genetics
-
Cell Hypoxia / physiology
-
Cell Line, Tumor
-
Cell Movement / genetics
-
Cell Movement / physiology
-
Endothelium, Vascular / cytology
-
Endothelium, Vascular / metabolism
-
Endothelium, Vascular / physiology
-
Gene Expression Regulation, Neoplastic / genetics
-
Gene Expression Regulation, Neoplastic / physiology*
-
Humans
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
Kidney Neoplasms / genetics
-
Kidney Neoplasms / metabolism
-
Kidney Neoplasms / pathology
-
RNA, Small Interfering / genetics
-
Trans-Activators / antagonists & inhibitors
-
Trans-Activators / biosynthesis
-
Trans-Activators / genetics
-
Trans-Activators / physiology*
-
Transcription Factors / antagonists & inhibitors
-
Transcription Factors / biosynthesis
-
Transcription Factors / genetics
-
Transcription Factors / physiology*
-
Transcriptional Activation / genetics
-
Transcriptional Activation / physiology*
-
Transfection
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
HIF1A protein, human
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
RNA, Small Interfering
-
Trans-Activators
-
Transcription Factors
-
endothelial PAS domain-containing protein 1