Cancer-Specific Activation of the Survivin Promoter and Its Potential Use in Gene Therapy

Survivin is expressed in many cancers but not in normal adult tissues and is
transcriptionally regulated. To test the feasibility of using the survivin promoter to
induce cancer-specific transgene expression in lung cancer gene therapy, a vector
expressing a luciferase gene driven by the survivin promoter was constructed and
evaluated in vitro and in vivo. We found that the survivin promoter was generally
more highly activated in cancer cell lines than in normal and immortalized normal cell
lines. When delivered intravenously by DNA:liposome complexes, the survivin
promoter was more than 200 times more cancer specific than the cytomegalovirus
promoter in vivo. To identify lung cancer patients who may benefit from gene therapy
with the survivin promoter, we measured survivin protein expression in surgical
specimens of 75 non-small-cell lung cancers and 10 normal lung tissues by
immunohistochemical staining and found that survivin is expressed in most of the
non-small-cell lung cancers tested (81%, 61 of 75) but none of the normal lung tissues.
The survivin promoter also induced transgene expression of a mutant Bik in cancer
cells, which suppressed the growth of cancer cells in vitro and in vivo. These results
indicate that the survivin promoter is a cancer-specific promoter for various cancers
and that it may be useful in cancer gene therapy.