Target gene therapy of glioma: overexpression of BAX gene under the control of both tissue-specific promoter and hypoxia-inducible element.
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.
Huang
Jiwei
J
Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Gao
Jun
J
Lv
Xiang
X
Li
Guilin
G
Hao
Delong
D
Yao
Xiaoying
X
Zhou
Liquan
L
Liu
Depei
D
Wang
Renzhi
R
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*
C494826:BAX protein, human; D005904:Glial Fibrillary Acidic Protein; D051793:Hypoxia-Inducible Factor 1; D051028:bcl-2-Associated X Protein