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.

BACKGROUND: Preoperative radiotherapy reduces the rate of local recurrence and improves the chance of survival in patients with resectable, advanced rectal carcinoma. However, because not all tumors respond similarly to radiation, sorting out suitable patients is required to irradiate tumors rationally. The authors examined the possible role of Ku protein in determining tumor radiosensitivity and disease free survival in patients with rectal carcinoma.METHODS: The authors studied 96 patients with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, the number of cells that were stained positive for Ku protein was evaluated by immunohistochemistry. The expression pattern of Ku protein was examined for an association between tumor radiosensitivity (which was determined according to T classification downstaging, complete pathologic response, or Response Evaluation Criteria in Solid Tumors) and disease free survival.RESULTS: There was a high degree of correlation between the percentage of cells that expressed the 70‐kDa Ku protein (Ku70) and the 86‐kDa Ku protein (Ku86) in the tumor sections (correlation coefficient = 0.85; P < 0.001). The expression pattern of Ku protein was correlated not only with tumor radiosensitivity but also with disease free survival. Pathologic TMN classification, histopathologic grade, and Ku70 expression were significant prognostic variables for disease free survival in a multivariate analysis (P = 0.0031, P = 0.030, and P = 0.023, respectively).CONCLUSIONS: Ku70 and Ku86 raise the predictive possibility of tumor radiosensitivity. Ku may be a useful parameter for selecting patients with rectal carcinoma for preoperative radiotherapy. Cancer 2002;95:1199–205. © 2002 American Cancer Society.DOI 10.1002/cncr.10807