Targeting gene expression to hypoxic tumor cells.

Journal article

Solid tumors with areas of low oxygen tension (hypoxia) have a poor prognosis, as cells in this environment often survive radiation and chemotherapy. In this report we describe how this hypoxic environment can be used to activate heterologous gene expression driven by a hypoxia-responsive element (HRE), which interacts with the transcriptional complex hypoxia-inducible factor-1 (HIF-1). Our results demonstrate that the HIF-1/HRE system of gene regulation is active in hypoxic tumor cells and show the potential of exploiting tumor-specific conditions for the targeted expression of diagnostic or therapeutic genes in cancer therapy.

Authors: Dachs, G; Patterson, A; Firth, J; Ratcliffe, P; Townsend, K

• Publication status: Published
• Journal: Nature medicine
• Volume: 3
• Issue: 5
• Pages: 515-520
• Publication date: 1997-05-01
• DOI: 10.1038/nm0597-515
• EISSN: 1546-170X
• ISSN: 1078-8956
• Language: English
• Keywords: Fibrosarcoma; Genes, Reporter; Misonidazole; Recombinant Fusion Proteins; Fluorouracil; Humans; DNA-Binding Proteins; Oxygen; Phosphoglycerate Kinase; Cytosine Deaminase; Tumor Cells, Cultured; Nucleoside Deaminases; Animals; Promoter Regions, Genetic; Mice, Nude; Mice; Transcription Factors; Antimetabolites, Antineoplastic; Hypoxia-Inducible Factor 1, alpha Subunit; Cell Hypoxia; Nuclear Proteins; Prodrugs; Neoplasm Transplantation; Hypoxia-Inducible Factor 1; Gene Expression Regulation, Neoplastic; Flucytosine