title: Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.
abstract: Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog) promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373). Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk) driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.
authors.affiliation: Stroke Center, The Affiliated Shenzhen Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.|Department of Neurology, The Affiliated Shenzhen Nanshan Hospital, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Neurosurgery, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Stroke Center, The Affiliated Shenzhen Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong, China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Stroke Center, The Affiliated Shenzhen Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Song
authors.affiliation: Stroke Center, The Affiliated Shenzhen Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen Guangdong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: Stroke Center, The Affiliated Shenzhen Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.
authors.forename: Baojin
authors.initials: B
authors.lastname: Zhai
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D005260:Female; D017930:Genes, Reporter; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000378:metabolism / Q000627:therapeutic use; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D013937:Thymidine Kinase