Nature Medicine
3, 515 - 520 (1997)
doi:10.1038/nm0597-515
Targeting gene expression to hypoxic tumor cellsGabi U. Dachs1, 2, Adam V. Patterson1, 3, 4, John D. Firth5, 6, Peter. J. Ratcliffe5, K.M. Stuart Townsend1, Ian. J. Stratford1, 4, 7
& Adrian L. Harris3
1Experimental Oncology Division, Medical Research Council, Harwell, OX11 ORD, UK
2Gray Laboratory, Mount Vemon Hospital, Northwood, HA6 2JR, UK
3Imperial Cancer Research Fund Molecular Oncology Laboratory, Institute of Molecular Medicine, John Raddiffe Hospital, Oxford, OX3 9DU, UK
4School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, M13 9PL, UK
5Erythropoietin Group, Institute of Molecular Medicine, John Raddiffe Hospital, Oxford, OX3 9DU, UK
6Addenbrooks Hospital, Cambridge, CB2 2QG, UK
7Correspondence should be addressed to I.J.S. at the University of Manchester Solid tumors with areas of low oxygen tension (hypoxia) have a poor prognosis, as celts 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.
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