Gene therapy is a novel
therapy for
melanoma. To date, however, there is still no powerful
tumor specific promoter (TSP) to restrict the transgene expression in
melanoma cells. In order to define a useful TSP for targeting in the context of
melanoma gene therapy, four promoters, the
cyclooxygenase-2 (Cox-2),
alpha-chemokine SDF-1
receptor (CXCR4), epithelial
glycoprotein 2 (EGP-2), and
survivin, were tested in both established
melanoma cell lines and primary
melanoma cells. We employed recombinant adenoviral vectors (reAds) each with a candidate TSP (the Cox-2, CXCR4, EGP-2, or
survivin), a reporter
luciferase gene, and a
poly-A signal, all of which were inserted into the E1-deleted region. A reAdGL3Bcytomegalovirus (CMV), containing the CMV promoter and
luciferase gene, was used as a positive control to normalize the
luciferase activity.
Luciferase activity was measured in multiple tumor cell lines and two primary
melanoma cell cultures after
infection with reAds. Human epithelial melanocytes, HEM, were used as normal control. In contrast to three other promoters, the
survivin promoter exhibited the highest activities within both
melanoma cell lines and primary
melanoma cells, but not in HEMs. Additionally, the
survivin promoter exhibited very low activities in major mouse organs including the liver, in vivo. EGP-2 is not active in
melanoma;
messenger RNA expressions were correlated to promoter activities both in
melanoma cell lines and primary cell cultures. Thus, these data suggest that the
survivin promoter achieved a '
tumor-on/liver-off' profile, and thus represents a potentially useful
tumor-specific promoter with applications for transcriptional targeting of Ad vector-based cancer gene
therapy or oncolysis to
melanoma.