Up-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancer.

Yoshio Hosoi, Toshiaki Watanabe, Keiichi Nakagawa, Yoshihisa Matsumoto, Atsushi Enomoto, Akinori Morita, Hirokazu Nagawa, Norio Suzuki

Research output: Contribution to journalArticlepeer-review

141 Citations (Scopus)

Abstract

Tumor tissues and adjacent normal tissues in 12 colorectal cancers were examined for quantitative differences in: i) activity of DNA-dependent protein kinase (DNA-PK), which functions in DNA double-strand breads repair, and ii) protein and mRNA levels of Ku70, Ku80, DNA-PKcs and transcriptional factor Sp1. DNA-PK activity and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1 were significantly higher in the tumor tissues compared with the normal tissues. Significant correlations between DNA-PK activity and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1 were observed. Because Ku80 and DNA-PKcs have consensus Sp1 recognition elements in their promoter region, the DNA sequence of Ku70 promoter region was analyzed. Analysis of Ku70 promoter region reveled that Ku70 gene has consensus Sp1 recognition elements in its promoter region. mRNA levels of Ku70, Ku80 and DNA-PKcs were correlated with one another, and significant correlations between Sp1 protein level and mRNA levels of Ku70 and Ku80 were observed. These results suggest that DNA-PK activity and protein- and mRNA-levels of Ku70, Ku80 and DNA-PKcs were elevated in tumor tissues in patients with colorectal cancer because of elevated Sp1 protein levels in tumor tissues.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalInternational journal of oncology
Volume25
Issue number2
DOIs
Publication statusPublished - 2004 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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