Detection of Endogenous DNA Double-strand Breaks in Oral Squamous Epithelial Lesions by P53-binding Protein 1

被引:6
|
作者
Imaizumi, Toshinobu [1 ,2 ]
Matsuda, Katsuya [1 ]
Tanaka, Kei [2 ]
Kondo, Hisayoshi [3 ]
Ueki, Nozomi [1 ]
Kurohama, Hirokazu [1 ]
Otsubo, Chieko [1 ]
Matsuoka, Yuki [1 ]
Akazawa, Yuko [1 ]
Miura, Shiro [4 ]
Nakashima, Masahiro [1 ]
机构
[1] Nagasaki Univ, Grad Sch Biomed Sci, Atom Bomb Dis Inst, Dept Tumor & Diagnost Pathol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan
[2] Nagasaki Univ Hosp, Dept Diagnost Pathol, Nagasaki, Japan
[3] Nagasaki Univ, Atom Bomb Dis Inst, Div Sci Data Registry, Biostat Sect, Nagasaki, Japan
[4] Natl Hosp Org Nagasaki Med Ctr, Dept Diagnost Pathol, Nagasaki, Japan
关键词
53BP1; genome instability; immunofluorescence; oral cancer; tumor biomarkers; POTENTIALLY MALIGNANT DISORDERS; CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS; NUCLEAR FOCI; 53BP1; CANCER; HEAD; TRANSFORMATION; DYSPLASIA; CAVITY;
D O I
10.21873/anticanres.15292
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: P53-binding protein 1 (53BP1) is one of the DNA damage response (DDR) molecules. This study aimed to assess 53BP1 expression by immunofluorescence (IF) as a biomarker to differentiate between oral squamous epithelial lesions (OSELs). Materials and Methods: We analyzed 129 archival oral biopsy samples, including 18 benign squamous lesions (BSLs), 37 low-grade dysplasias (LGDs), 22 high-grade dysplasias (HGDs), and 52 oral squamous cell carcinomas (OSCCs). 53BP1 and Ki-67 expressions were examined by double IF to assess the type of 53BP1 expression. Results: We found that OSCC exhibited several 53BP1 nuclear foci, particularly high-DNA damage response (HDDR) and large focus (LF)-type, suggesting the presence of endogenous DNA double-strand breaks in the cancer genome, which could disrupt DDR and induce genomic injury. We also found a difference in 53BP1 expression between LGD and HGD, but not between BSL and LGD. Among the Ki-67-positive cells, HDDR- and LF-type expressions were higher in OSELs of higher grades. Conclusion: 53BP1 expression can be a valuable biomarker for OSELs to help estimate the grade of oral epithelial dysplasia.
引用
收藏
页码:4771 / 4779
页数:9
相关论文
共 50 条
  • [31] Clioquinol induces DNA double-strand breaks, activation of ATM, and subsequent activation of p53 signaling
    Katsuyama, Masato
    Iwata, Kazumi
    Ibi, Masakazu
    Matsuno, Kuniharu
    Matsumoto, Misaki
    Yabe-Nishimura, Chihiro
    TOXICOLOGY, 2012, 299 (01) : 55 - 59
  • [32] p53 protects from replication-associated DNA double-strand breaks in mammalian cells
    Kumari, A
    Schultz, N
    Helleday, T
    ONCOGENE, 2004, 23 (13) : 2324 - 2329
  • [33] p53 protects from replication-associated DNA double-strand breaks in mammalian cells
    Anuradha Kumari
    Niklas Schultz
    Thomas Helleday
    Oncogene, 2004, 23 : 2324 - 2329
  • [34] UCN-01 and camptothecin induce DNA double-strand breaks in p53 mutant tumor cells, but not in normal or p53 negative epithelial cells
    Jones, CB
    Clements, MK
    Redkar, A
    Daoud, SS
    INTERNATIONAL JOURNAL OF ONCOLOGY, 2000, 17 (05) : 1043 - 1051
  • [35] HIV-1 Vpr induces DNA double-strand breaks
    Tachiwana, H
    Shimura, M
    Nakai-Murakami, C
    Tokunaga, K
    Takizawa, Y
    Sata, T
    Kurumizaka, H
    Ishizaka, Y
    CANCER RESEARCH, 2006, 66 (02) : 627 - 631
  • [36] Beclin1 promotes DNA double-strand breaks repair
    Xu, Fei
    Yan, Lili
    Wang, Jianrong
    Yang, Jinming
    CANCER RESEARCH, 2017, 77
  • [37] Accumulation of Ku70 at DNA double-strand breaks in living epithelial cells
    Koike, Manabu
    Yutoku, Yasutomo
    Koike, Aki
    EXPERIMENTAL CELL RESEARCH, 2011, 317 (17) : 2429 - 2437
  • [38] Chromosomal aberrations induced by defined DNA double-strand breaks: The origin of achromatic lesions
    Harvey, AN
    Costa, ND
    Savage, JRK
    Thacker, J
    SOMATIC CELL AND MOLECULAR GENETICS, 1997, 23 (03) : 211 - 219
  • [39] PARP activation regulates the RNA-binding protein NONO in the DNA damage response to DNA double-strand breaks
    Krietsch, Jana
    Caron, Marie-Christine
    Gagne, Jean-Philippe
    Ethier, Chantal
    Vignard, Julien
    Vincent, Michel
    Rouleau, Michele
    Hendzel, Michael J.
    Poirier, Guy G.
    Masson, Jean-Yves
    NUCLEIC ACIDS RESEARCH, 2012, 40 (20) : 10287 - 10301
  • [40] Endonucleolytic processing of covalent protein-linked DNA double-strand breaks
    Matthew J. Neale
    Jing Pan
    Scott Keeney
    Nature, 2005, 436 : 1053 - 1057