title: Novel, chimeric, cancer-specific, and radiation-inducible gene promoters for suicide gene therapy of cancer.
abstract: BACKGROUND
  Although the promoter of the human telomerase reverse transcriptase (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it has some limitations for clinical use because of its low activity and potential toxicity to certain normal cells. To overcome these defects, the authors generated novel chimeric hTERT promoters that contained the radiation-inducible sequence CC(A/T)(6) GG (known as CArG elements).
  
  
  METHODS
  Chimeric hTERT promoters were synthesized that contained different numbers of CArG elements, and the activity of chimeric promoters was assessed in different cancer cell lines and normal cells. The potential of selected promoters to successfully control horseradish peroxidase (HRP) and prodrug indole-3-acetic acid (IAA) suicide gene therapy was tested in vitro and in vivo.
  
  
  RESULTS
  The promoter activity assays indicated that the synthetic promoter that contained 6 repeating CArG units had the best radiation inducibility than any other promoters that contained different numbers of CArG units, and the chimeric promoters retained their cancer-specific characteristics. The chimeric promoter was better at driving radiation-inducible gene therapy than the control promoters. The sensitizer enhancement ratio of the chimeric promoter system determined by clonogenic assay was higher, and the chimeric promoter system resulted in a significantly higher apoptotic level compared with other promoter systems. The combination of chimeric/promoter-mediated gene therapy and radiotherapy significantly inhibited tumor volume in a xenograft mouse model and resulted in a significant prolongation of survival in mice.
  
  
  CONCLUSIONS
  The current results indicated that a combinational cancer-specific promoter system that is responsive to irradiation has great potential for improving the efficacy of cancer treatment.
authors: Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors: Jie
authors: J
authors: Xiong
authors: Wen-Jie
authors: WJ
authors: Sun
authors: Wei-Feng
authors: WF
authors: Wang
authors: Zheng-Kai
authors: ZK
authors: Liao
authors: Fu-Xiang
authors: FX
authors: Zhou
authors: Hai-Yan
authors: HY
authors: Kong
authors: Yu
authors: Y
authors: Xu
authors: Cong-Hua
authors: CH
authors: Xie
authors: Yun-Feng
authors: YF
authors: Zhou
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D004274:DNA, Recombinant; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D027602:Serum Response Element; D019098:Telomerase / Q000235:genetics* / Q000528:radiation effects*; D014183:Transplantation, Heterologous
chemical_list: D004274:DNA, Recombinant; C509186:TERT protein, human; D019098:Telomerase