title: [DNA  damage caused by suicide gene therapy system  under Tet-On regulation in breast cancer cells].
abstract: OBJECTIVE
  To determine the effect and molecular mechanism of DNA damage caused by suicide gene therapy system HSV-TK/GCV under Tet-On regulation in human breast cancer cell line MCF-7 infected by recombinant adeno-associated virus (rAAV).
  
  
  METHODS
  We used comet assay to detect the effect of HSV-TK/GCV suicide gene regulation system on MCF-7 DNA damage, and analyzed the expression change of relative DNA damage response active genes and proteins with RT-PCR and Western blot.
  
  
  RESULTS
  Compared with other control groups, the comet assay showed that MCF-7 cells with HSV-TK/GCV treatment had obvious comet tails, and the expression level of DNA damage response active genes and proteins changed obviously in the HSV-TK/GCV treatment group,such as ATM, p53 and p27,but CyclinE and CDK2 did not change.
  
  
  CONCLUSIONS
  DNA damage on MCF-7 cells is resulted from HSV-TK/GCV in suicide gene therapy system through a p53-dependent signal pathway, causing cell cycle arrest and cell death.
authors.affiliation: Molecular Biology Research Center, School of Biological Science and Technology, Central South University, Changsha, China.
authors.forename: Hongde
authors.initials: H
authors.lastname: Li
authors.forename: Shengguang
authors.initials: S
authors.lastname: Xiang
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.forename: Weixin
authors.initials: W
authors.lastname: Hu
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zeng
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004249:DNA Damage; D000229:Dependovirus / Q000235:genetics; D005260:Female; D015774:Ganciclovir / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D061986:MCF-7 Cells; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D011993:Recombinant Fusion Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir