Heterogeneous expression of DNA-dependent protein kinase in esophageal cancer and normal epithelium

Norio Tonotsuka, Yoshio Hosoi, Shukichi Miyazaki, Go Miyata, Ko Sugawara, Takahiro Mori, Noriaki Ouchi, Susumu Satomi, Yoshihisa Matsumoto, Keiichi Nakagawa, Kiyoshi Miyagawa, Tetsuya Ono

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Esophageal cancer tissues and adjacent normal mucosae in 13 patients with primary esophageal cancer were examined for quantitative differences in DNA-dependent protein kinase (DNA-PK) activity and for expressions of Ku70, Ku80 and DNA-PKcs proteins by Western blotting and immunohistochemistry. The tumor tissues showed higher DNA-PK activity than the normal mucosae. Protein levels of Ku70, Ku80 and DNA-PKcs correlated with DNA-PK activities in the tumor tissues. Immunohistochemical analysis revealed that Ku70, Ku80 and DNA-PKcs located predominantly in the nuclei in both the tumor tissues and normal mucosae. In the normal epithelium, Ku70, Ku80 and DNA-PKcs were expressed only in the nuclei of the basal cell layers and not in those of the lumenal cell layers. In the tumor tissues, the expressions of DNA-PK proteins showed intratumoral heterogeneity. The different portions in the same tumor showed different expression levels of DNA-PK proteins, and even each tumor cell showed different expression levels. These results suggest that cell differentiation and tumor progression affect cellular DNA-PK protein levels and its activity. Furthermore, the intratumoral heterogeneity of DNA-PK protein expression in esophageal cancer cells/tissues also suggests the difficulty in prediction of radio- or chemo-sensitivity of the tumor through estimation of DNA-PK activity/protein levels in tumor specimens.

Original languageEnglish
Pages (from-to)441-447
Number of pages7
JournalInternational journal of molecular medicine
Volume18
Issue number3
DOIs
Publication statusPublished - 2006 Sep

Keywords

  • DNA-PKcs
  • DNA-dependent protein kinase
  • Esophageal cancer
  • Ku70
  • Ku80

ASJC Scopus subject areas

  • Genetics

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