title: Target gene therapy of glioma: overexpression of BAX gene under the control of both tissue-specific promoter and hypoxia-inducible element.
abstract: Glioma-specific transcription of tumor-killing genes has been exploited as a promising gene therapeutic modality in glioma patients. Musashi1 (Msi1) and GFAP gene promoters are both cancer-specific promoters. Optimized HIF-binding site (optHBS) sequence was newly found as efficient as EPO HREs used as enhancer in cancer gene therapy. We constructed 4optHBS-Msi1/GFAP promoters and tested their ability to mediate BAX expression to induce apoptosis in glioma cell lines. Our results demonstrated that 4optHBS-Msi1/GFAP promoters are apparently strong and glioma-selective promoters with potential application in targeted glioma gene therapy, and 4optHBS-Msi1/GFAPBAXa are valuable tools for glioma gene therapy.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Xiang
authors.initials: X
authors.lastname: Lv
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
authors.forename: Delong
authors.initials: D
authors.lastname: Hao
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yao
authors.forename: Liquan
authors.initials: L
authors.lastname: Zhou
authors.forename: Depei
authors.initials: D
authors.lastname: Liu
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D001665:Binding Sites; D001932:Brain Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D005434:Flow Cytometry / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005910:Glioma / Q000628:therapy*; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494826:BAX protein, human; D005904:Glial Fibrillary Acidic Protein; D051793:Hypoxia-Inducible Factor 1; D051028:bcl-2-Associated X Protein