Time-course analysis of DNA damage response-related genes after in vitro radiation in H460 and H1229 lung cancer cell lines

被引:18
作者
Kim, Kang Ho [2 ,3 ,4 ]
Yoo, Hae Yong [3 ]
Joo, Kyeung Min [4 ,5 ]
Jung, Yong [2 ,3 ,4 ]
Jin, Juyoun [2 ,3 ,4 ]
Kim, Yonghyun [2 ,3 ,4 ]
Yoon, Su Jin [3 ]
Choi, Seung Ho [3 ]
Seol, Ho Jun [2 ,3 ,4 ]
Park, Woong-Yang [1 ]
Nam, Do-Hyun [2 ,3 ,4 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Biomed Sci Biochem & Mol Biol, Seoul 110799, South Korea
[2] Sungkyunkwan Univ, Sch Med, Dept Neurosurg, Seoul 135710, South Korea
[3] Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Seoul 135710, South Korea
[4] Sungkyunkwan Univ, Sch Med, Canc Stem Cell Res Ctr, Samsung Med Ctr, Seoul 135710, South Korea
[5] Seoul Natl Univ, Coll Med, Dept Anat, Seoul 110799, South Korea
关键词
carcinoma; non-small-cell lung; DNA damage; gene expression profiling; microarray analysis; radiation; tumor suppressor protein p53; WILD-TYPE P53; CONSTITUTIVE ACTIVATION; EXPRESSION; ATM; IRRADIATION; KINASES; APOPTOSIS; COMPLEX; STRESS; TOPBP1;
D O I
10.3858/emm.2011.43.7.046
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Radiation is the most useful treatment modality for cancer patients. It initiates a series of signal cascades such as DNA damage response (DDR) signaling for repairing damaged DNA, arresting the cell cycle, and inducing cell death. Until now, few genes have been found to be regulated by radiation, which explains the molecular mechanisms of cellular responses to radiation. Although the transcriptional changes caused by radiation have been widely investigated, little is known about the direct evidence for the transcriptional control of DDR-related genes. Here, we examined the radiosensitivity of two non-small cell lung cancer cell lines (H460 and H1299), which have different p53 status. We monitored the time-dependent changes of 24 DDR-related gene expressions via microarray analysis. Based on the basal expression levels and temporal patterns, we further classified 24 DDR-related genes into four subgroups. Then, we also addressed the protein levels of several DDR-related genes such as TopBP1, Chk1 and Chk2, confirming the results of microarray analysis. Together, these results indicate that the expression patterns of DDR-related genes are associated with radiosensitivity and with the p53 statuses of H460 and H1299, which adds to the understanding of the complex biological responses to radiation.
引用
收藏
页码:419 / 426
页数:8
相关论文
共 32 条
  • [1] Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses
    Amundson, SA
    Bittner, M
    Chen, YD
    Trent, J
    Meltzer, P
    Fornace, AJ
    [J]. ONCOGENE, 1999, 18 (24) : 3666 - 3672
  • [2] Chk1 and Chk2 kinases in checkpoint control and cancer
    Bartek, J
    Lukas, J
    [J]. CANCER CELL, 2003, 3 (05) : 421 - 429
  • [3] DNA damage response mediators MDC1 and 53BP1:: constitutive activation and aberrant loss in breast and lung cancer, but not in testicular germ cell tumours
    Bartkova, J.
    Horejsi, Z.
    Sehested, M.
    Nesland, J. M.
    Rajpert-De Meyts, E.
    Skakkebaek, N. E.
    Stucki, M.
    Jackson, S.
    Lukas, J.
    Bartek, J.
    [J]. ONCOGENE, 2007, 26 (53) : 7414 - 7422
  • [4] Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas
    Bartkova, J.
    Hamerlik, P.
    Stockhausen, M-T
    Ehrmann, J.
    Hlobilkova, A.
    Laursen, H.
    Kalita, O.
    Kolar, Z.
    Poulsen, H. S.
    Broholm, H.
    Lukas, J.
    Bartek, J.
    [J]. ONCOGENE, 2010, 29 (36) : 5095 - 5102
  • [5] Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Bartkova, Jirina
    Rezaei, Nousin
    Liontos, Michalis
    Karakaidos, Panagiotis
    Kletsas, Dimitris
    Issaeva, Natalia
    Vassiliou, Leandros-Vassilios F.
    Kolettas, Evangelos
    Niforou, Katerina
    Zoumpourlis, Vassilis C.
    Takaoka, Munenori
    Nakagawa, Hiroshi
    Tort, Frederic
    Fugger, Kasper
    Johansson, Fredrik
    Sehested, Maxwell
    Andersen, Claus L.
    Dyrskjot, Lars
    Orntoft, Torben
    Lukas, Jiri
    Kittas, Christos
    Helleday, Thomas
    Halazonetis, Thanos D.
    Bartek, Jiri
    Gorgoulis, Vassilis G.
    [J]. NATURE, 2006, 444 (7119) : 633 - 637
  • [6] Enhanced induction of Bax gene expression in H460 and H1299 cells with the combined treatment of cisplatin and adenovirus mediated wt-p53 gene transfer
    Choi, JH
    Ahn, KS
    Kim, J
    Hong, YS
    [J]. EXPERIMENTAL AND MOLECULAR MEDICINE, 2000, 32 (01) : 23 - 28
  • [7] Specificity protein 1-dependent p53-mediated suppression of human manganese superoxide dismutase gene expression
    Dhar, Sanjit Kumar
    Xu, Yong
    Chen, Yumin
    Clair, Daret K. St.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (31) : 21698 - 21709
  • [8] DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?
    Durocher, D
    Jackson, SP
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2001, 13 (02) : 225 - 231
  • [9] Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
    Falck, J
    Coates, J
    Jackson, SP
    [J]. NATURE, 2005, 434 (7033) : 605 - 611
  • [10] LIN28B confers radio-resistance through the posttranscriptional control of KRAS
    Jeong, Sun-Hye
    Wu, Hong-Gyun
    Park, Woong-Yang
    [J]. EXPERIMENTAL AND MOLECULAR MEDICINE, 2009, 41 (12) : 912 - 918