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.
Chen
Jin-Shing
JS
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Liu
Jaw-Ching
JC
Shen
Lei
L
Rau
Kung-Ming
KM
Kuo
Hsu-Ping
HP
Li
Yan M
YM
Shi
Daren
D
Lee
Yung-Chie
YC
Chang
King-Jen
KJ
Hung
Mien-Chie
MC
D001483:Base Sequence; D017931:DNA Primers; D015316:Genetic Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins; D010957:Plasmids; D011401:Promoter Regions, Genetic; D000077022:Survivin; D014162:Transfection; D019076:Transgenes
C107489:BIRC5 protein, human; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin