Journal Article

The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer

Masanori Someya, Koh-ichi Sakata, Yoshihisa Matsumoto, Hiroyuki Yamamoto, Manami Monobe, Hideyuki Ikeda, Koichi Ando, Yoshio Hosoi, Norio Suzuki and Masato Hareyama

in Carcinogenesis

Volume 27, issue 1, pages 117-122
Published in print January 2005 | ISSN: 0143-3334
Published online July 2005 | e-ISSN: 1460-2180 | DOI:
The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer

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The DNA double-strand breaks (DSBs) repair pathway has been implicated in maintaining genomic integrity via suppression of chromosomal rearrangements. DNA-dependent protein kinase (DNA-PK) has an important role with DNA DSBs repair. In this study, 93 of untreated cancer patients and 41 of cancer-free healthy volunteers were enrolled. Peripheral blood was collected, separated and centrifuged; DNA-PK activity was measured by DNA-pull-down assay. The expressions of DNA-PKcs, Ku70 and Ku86 were examined by RT–PCR assay and western blotting. Chromosomal aberrations were examined by cytogenetic methods. DNA-PK activities of peripheral blood lymphocytes (PBL) in patients with uterine cervix or breast cancer were significantly lower than those in normal volunteers. Age and smoking had no association with DNA-PK activity, whereas DNA-PK activity and the expression of Ku70, Ku86 and DNA-PKcs in RT–PCR were interrelated. A similar tendency was seen in western blot assay but less clear than in RT–PCR. Therefore, the association between DNA-PK activity and expression of DNA-PK in protein level could not be concluded. The frequency of chromosome aberration, such as dicentric chromosomes and excess fragment increased as the DNA-PK activity decreased. In conclusion, DNA-PK activity is associated with chromosomal instability. DNA-PK activity in PBL is associated with risk of breast and uterine cervix cancer. DNA-PK activity in PBL can be used to select individuals for whom an examination should be performed because of their increased susceptibility to breast and uterine cervix cancer.

Keywords: DNA-PK, DNA-dependent protein kinase; DSBs, double strand breaks; DNA-PKcs, DNA-PK catalytic subunit; HPV, human papilloma virus; HR, homologous recombination; NHEJ, non-homologous end-joining; PBL, peripheral blood lymphocytes; SNPs, single nucleotide polymorphisms

Journal Article.  4379 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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