title: Cancer-specific activation of the survivin promoter and its potential use in gene therapy.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Jin-Shing
authors.initials: JS
authors.lastname: Chen
authors.forename: Jaw-Ching
authors.initials: JC
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Kung-Ming
authors.initials: KM
authors.lastname: Rau
authors.forename: Hsu-Ping
authors.initials: HP
authors.lastname: Kuo
authors.forename: Yan M
authors.initials: YM
authors.lastname: Li
authors.forename: Daren
authors.initials: D
authors.lastname: Shi
authors.forename: Yung-Chie
authors.initials: YC
authors.lastname: Lee
authors.forename: King-Jen
authors.initials: KJ
authors.lastname: Chang
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: 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
chemical_list: C107489:BIRC5 protein, human; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin