RESEARCH ARTICLE

Correlativity study between expression of DNA double-strand break repair protein and radiosensitivity of tumor cells

  • Liang ZHUANG 1 ,
  • Shiying YU , 1 ,
  • Xiaoyuan HUANG 2 ,
  • Yang CAO 2 ,
  • Huihua XIONG 1
Expand
  • 1. Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 2. Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Received date: 02 Jul 2008

Accepted date: 10 Aug 2008

Published date: 05 Mar 2009

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

DNA double-strand break (DSB) is generally regarded as the most lethal of all DNA lesions after radiation. Ku80, DNA-PK catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) proteins are major DSB repair proteins. In this study, survival fraction at 2Gy (SF2) values of eight human tumor cell lines (including four human cervical carcinoma cell lines HeLa, SiHa, C33A, Caski, three human breast carcinoma cell lines MCF-7, MDA-MB-231, MDA-MB-453, and one human lung carcinoma cell line A549) were acquired by clone formation assay, and western blot was applied to detect the expressions of Ku80, DNA-PKcs and ATM protein. The correlativity of protein expression with SF2 value was analyzed by Pearson linear correlation analysis. We found that the expression of same protein in different cell lines and the expression of three proteins in the same cell line had a significant difference. The SF2 values were also different in eight tumor cell lines and there was a positive correlativity between the expression of DNA-PKcs and SF2 (r =0.723, P = 0.043), but Ku80 and ATM expression had no correlation with SF2 (P>0.05). These findings suggest that the expression level of DNA-PKcs protein can be an indicator for predicting the radiosensitivity of tumor cells.

Cite this article

Liang ZHUANG , Shiying YU , Xiaoyuan HUANG , Yang CAO , Huihua XIONG . Correlativity study between expression of DNA double-strand break repair protein and radiosensitivity of tumor cells[J]. Frontiers of Medicine, 2009 , 3(1) : 26 -29 . DOI: 10.1007/s11684-009-0008-7

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 30672426).
1
Van GentD C, HoeijmakersJ H, KanaarR. Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet, 2001, 2(3): 196–206

DOI

2
WeteringsE, ChenD J. DNA-dependent protein kinase in nonhomologous end joining: a lock with multiple keys?J Cell Biol, 2007, 179(2): 183–186

DOI

3
CollisS J, DeWeeseT L, JeggoP A, ParkerA R. The life and death of DNA-PK. Oncogene, 2005, 24(6): 949–961

DOI

4
LieberM R, MaY, PannickeU, SchwarzK. Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol, 2003, 4(9): 712–720

DOI

5
ValerieK, PovirkL F. Regulation and mechanisms of mammalian double-strand break repair. Oncogene, 2003, 22(37): 5792–5812

DOI

6
WalkerJ R, CorpinaR A, GoldbergJ. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature, 2001, 412(6847): 607–614

DOI

7
DipR, NaegeliH. More than just strand breaks: the recognition of structural DNA discontinuities by DNA-dependent protein kinase catalytic subunit. FASEB J, 2005, 19(7): 704–715

DOI

8
BudmanJ, ChuG. Processing of DNA for nonhomologous end-joining by cell-free extract. EMBO J, 2005, 24(4): 849–860

DOI

9
BoskovicJ, Rivera-CalzadaA, MamanJ D, ChacónP, WillisonK R, PearlL H, LlorcaO. Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. EMBO J, 2003, 22(21): 5875–5882

DOI

10
PawelczakK S, TurchiJ J. A mechanism for DNA-PK activation requiring unique contributions from each strand of a DNA terminus and implications for microhomology-mediated nonhomologous DNA end joining. Nucleic Acids Res, 2008, 36(12): 4022–4031

DOI

11
SakataK, SomeyaM, MatsumotoY, HareyamaM. Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity. Radiat Med, 2007, 25(9): 433–438

DOI

12
ZhuangL, YuS Y, HuangX Y, GaoQ L, XiongH, LengY. Effect of Ku80 expression inhibition by RNA interference on proliferation of cervical carcinoma cell line HeLa. Ai Zheng, 2007, 26(3): 252–257 (in Chinese)

13
RampakakisE, Di PaolaD, Zannis-HadjopoulosM. Ku is involved in cell growth, DNA replication and G1-S transition. J Cell Sci, 2008, 121(Pt 5): 590–600

DOI

14
HsuH L, GilleyD, GalandeS A, HandeM P, AllenB, KimS H, LiG C, CampisiJ, Kohwi-ShigematsuT, ChenD J. Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev, 2000, 14(22): 2807–2812

DOI

15
BaileyS M, BrennemanM A, HalbrookJ, NickoloffJ A, UllrichR L, GoodwinE H. The kinase activity of DNA-PK is required to protect mammalian telomeres. DNA Repair (Amst), 2004, 3(3): 225–233

DOI

16
SirzenF, NilssonA, ZhivotovskyB, LewensohnR. DNA-dependent protein kinase content and activity in lung carcinoma cell lines: correlation with intrinsic radiosensitivity. Eur J Cancer, 1999, 35(1): 111–116

DOI

17
ShintaniS, MiharaM, LiC, NakaharaY, HinoS, NakashiroK, HamakawaH. Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma. Cancer Sci, 2003, 94(10): 894–900

DOI

18
ZhaoH J, HosoiY, MiyachiH, IshiiK, YoshidaM, NemotoK, TakaiY, YamadaS, SuzukiN, OnoT. DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines. Clin Cancer Res, 2000, 6(3): 1073–1078

19
MorioT, KimH. Ku, Artemis, and ataxia-telangiectasia-mutated: signalling networks in DNA damage. Int J Biochem Cell Biol, 2008, 40(4): 598–603

DOI

20
BurmaS, ChenD J. Role of DNA-PK in the cellular response to DNA double-strand breaks. DNA Repair (Amst), 2004, 3(8-9): 909–918

DOI

21
HammarstenO, ChuG. DNA-dependent protein kinase: DNA binding and activation in the absenceβofβKu. Proc Natl Acad Sci USA, 1998, 95(2): 525–530

DOI

22
WestR B, YanevaM, LieberM R. Productive and nonproductive complexes of Ku and DNA-dependent protein kinase at DNA termini. Mol Cell Biol, 1998, 18(10): 5908–5920

23
SallesB, CalsouP, FritP, MullerC. The DNA repair complex DNA-PK, a pharmacological target in cancer chemotherapy and radiotherapy. Pathol Biol (Paris), 2006, 54(4): 185–193

DOI

24
KelleyM R, FishelM L. DNA repair proteins as molecular targets for cancer therapeutics. Anticancer Agents Med Chem, 2008, 8(4): 417–425

Options
Outlines

/