The Association of Dna-dependent Protein Kinase Activity with Chromosomal Instability and Risk of Cancer.
From: Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.
Carcinogenesis
- Publish Date: Jan 2006
- ISSN: 0143-3334
- Volume: 27
- Issue: 1
- Pages: 117-22
- Medium: Print
- Language: English
- Citation (JAMA): Someya Masanori, Sakata Koh-ichi, Matsumoto Yoshihisa, et al. The Association of Dna-dependent Protein Kinase Activity with Chromosomal Instability and Risk of Cancer.. Carcinogenesis Jan 2006;27:117-22
Abstract
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.
Mesh Headings (Keywords): Adult, Aged, Aged, 80 and over, Antigens, Nuclear, Blotting, Western, Breast Neoplasms, Case-Control Studies, Chromosomal Instability, Chromosome Aberrations, Cytogenetic Analysis, DNA Repair, DNA-Activated Protein Kinase, DNA-Binding Proteins, Esophageal Neoplasms, Female, Head and Neck Neoplasms, Humans, Lymphoma, Male, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, Smoking, Uterine Cervical Neoplasms
Check for Full Text / PubMed Unique Identifier (PMID): 16000400
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