DNA damage caused by suicide gene therapy system under Tet-On regulation in breast cancer cells.
10.3969/j.issn.1672-7347.2011.09.004
- Author:
Hongde LI
1
;
Shengguang XIANG
;
Nan MA
;
Weixin HU
;
Zhaojun ZENG
Author Information
1. Molecular Biology Research Center, School of Biological Science and Technology, Central South University, Changsha, China.
- Publication Type:Journal Article
- MeSH:
Breast Neoplasms;
genetics;
pathology;
therapy;
DNA Damage;
Dependovirus;
genetics;
Female;
Ganciclovir;
metabolism;
pharmacology;
Gene Expression Regulation, Neoplastic;
Genes, Transgenic, Suicide;
genetics;
Genetic Therapy;
Humans;
MCF-7 Cells;
Recombinant Fusion Proteins;
genetics;
metabolism;
Simplexvirus;
enzymology;
Thymidine Kinase;
genetics
- From:
Journal of Central South University(Medical Sciences)
2011;36(9):836-843
- CountryChina
- Language:Chinese
-
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.
CONCLUSION: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.
