Solid tumors with areas of low oxygen tension (hypoxia) have a poor pr
ognosis, as cells in this environment often survive radiation and chem
otherapy. In this report we describe how this hypoxic environment can
be used to activate heterologous gene expression driven by a hypoxia-r
esponsive element (HRE), which interacts with the transcriptional comp
lex hypoxia-inducible factor-1 (HIF-1). Our results demonstrate that t
he HIF-1/HRE system of gene regulation is active in hypoxic tumor cell
s and show the potential of exploiting tumor-specific conditions for t
he targeted expression of diagnostic or therapeutic genes in cancer th
erapy.