|
|
Correlativity study between expression of DNA double-strand break repair protein and radiosensitivity of tumor cells |
Liang ZHUANG1, Shiying YU1(), Xiaoyuan HUANG2, Yang CAO2, Huihua XIONG1 |
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 |
|
|
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.
|
Keywords
Ku80
DNA-PK(cs)-binding protein, human
ataxia telangiectasia mutated protein
tumor cell lines
radiosensitivity
|
Corresponding Author(s):
YU Shiying,Email:syy@tjh.tjmu.edu.cn
|
Issue Date: 05 March 2009
|
|
1 |
Van Gent D C, Hoeijmakers J H, Kanaar R. Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet , 2001, 2(3): 196–206 doi: 10.1038/35056049
|
2 |
Weterings E, Chen D J. DNA-dependent protein kinase in nonhomologous end joining: a lock with multiple keys?J Cell Biol , 2007, 179(2): 183–186 doi: 10.1083/jcb.200705106
|
3 |
Collis S J, DeWeese T L, Jeggo P A, Parker A R. The life and death of DNA-PK. Oncogene , 2005, 24(6): 949–961 doi: 10.1038/sj.onc.1208332
|
4 |
Lieber M R, Ma Y, Pannicke U, Schwarz K. Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol , 2003, 4(9): 712–720 doi: 10.1038/nrm1202
|
5 |
Valerie K, Povirk L F. Regulation and mechanisms of mammalian double-strand break repair. Oncogene , 2003, 22(37): 5792–5812 doi: 10.1038/sj.onc.1206679
|
6 |
Walker J R, Corpina R A, Goldberg J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature , 2001, 412(6847): 607–614 doi: 10.1038/35088000
|
7 |
Dip R, Naegeli H. 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: 10.1096/fj.04-3041rev
|
8 |
Budman J, Chu G. Processing of DNA for nonhomologous end-joining by cell-free extract. EMBO J , 2005, 24(4): 849–860 doi: 10.1038/sj.emboj.7600563
|
9 |
Boskovic J, Rivera-Calzada A, Maman J D, Chacón P, Willison K R, Pearl L H, Llorca O. Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. EMBO J , 2003, 22(21): 5875–5882 doi: 10.1093/emboj/cdg555
|
10 |
Pawelczak K S, Turchi J 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: 10.1093/nar/gkn344
|
11 |
Sakata K, Someya M, Matsumoto Y, Hareyama M. Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity. Radiat Med , 2007, 25(9): 433–438 doi: 10.1007/s11604-007-0161-3
|
12 |
Zhuang L, Yu S Y, Huang X Y, Gao Q L, Xiong H, Leng Y. 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 |
Rampakakis E, Di Paola D, Zannis-Hadjopoulos M. Ku is involved in cell growth, DNA replication and G1-S transition. J Cell Sci , 2008, 121(Pt 5): 590–600 doi: 10.1242/jcs.021352
|
14 |
Hsu H L, Gilley D, Galande S A, Hande M P, Allen B, Kim S H, Li G C, Campisi J, Kohwi-Shigematsu T, Chen D J. Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev , 2000, 14(22): 2807–2812 doi: 10.1101/gad.844000
|
15 |
Bailey S M, Brenneman M A, Halbrook J, Nickoloff J A, Ullrich R L, Goodwin E H. The kinase activity of DNA-PK is required to protect mammalian telomeres. DNA Repair (Amst) , 2004, 3(3): 225–233 doi: 10.1016/j.dnarep.2003.10.013
|
16 |
Sirzen F, Nilsson A, Zhivotovsky B, Lewensohn R. 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: 10.1016/S0959-8049(98)00289-5
|
17 |
Shintani S, Mihara M, Li C, Nakahara Y, Hino S, Nakashiro K, Hamakawa H. Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma. Cancer Sci , 2003, 94(10): 894–900 doi: 10.1111/j.1349-7006.2003.tb01372.x
|
18 |
Zhao H J, Hosoi Y, Miyachi H, Ishii K, Yoshida M, Nemoto K, Takai Y, Yamada S, Suzuki N, Ono T. 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 |
Morio T, Kim H. Ku, Artemis, and ataxia-telangiectasia-mutated: signalling networks in DNA damage. Int J Biochem Cell Biol , 2008, 40(4): 598–603 doi: 10.1016/j.biocel.2007.12.007
|
20 |
Burma S, Chen D J. Role of DNA-PK in the cellular response to DNA double-strand breaks. DNA Repair (Amst) , 2004, 3(8-9): 909–918 doi: 10.1016/j.dnarep.2004.03.021
|
21 |
Hammarsten O, Chu G. DNA-dependent protein kinase: DNA binding and activation in the absenceβofβKu. Proc Natl Acad Sci USA , 1998, 95(2): 525–530 doi: 10.1073/pnas.95.2.525
|
22 |
West R B, Yaneva M, Lieber M R. Productive and nonproductive complexes of Ku and DNA-dependent protein kinase at DNA termini. Mol Cell Biol , 1998, 18(10): 5908–5920
|
23 |
Salles B, Calsou P, Frit P, Muller C. The DNA repair complex DNA-PK, a pharmacological target in cancer chemotherapy and radiotherapy. Pathol Biol (Paris) , 2006, 54(4): 185–193 doi: 10.1016/j.patbio.2006.01.012
|
24 |
Kelley M R, Fishel M L. DNA repair proteins as molecular targets for cancer therapeutics. Anticancer Agents Med Chem , 2008, 8(4): 417–425
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|