Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

Gregory T. Langland, Steven M. Yannone, Rachel A. Langland, Aki Nakao, Yinghui Guan, Sydney B.T. Long, Lien Vonguyen, David J. Chen, Joe W. Gray, Fanqing Chen

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNA-PK in ovarian cancer.

Original languageEnglish (US)
Pages (from-to)1021-1026
Number of pages6
JournalOncology Reports
Volume23
Issue number4
DOIs
StatePublished - Apr 1 2010

Keywords

  • Apoptosis
  • Comparative genomic hybridization
  • DNA-PK
  • DNA-PKcs
  • Double-strand break repair
  • Ku
  • Ku70
  • Ku80
  • Ligase IV
  • Microarray
  • Non-homologous end joining
  • Ovarian cancer
  • Radioresistance
  • Radiosensitivity
  • XRCC4
  • p21
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Langland, G. T., Yannone, S. M., Langland, R. A., Nakao, A., Guan, Y., Long, S. B. T., Vonguyen, L., Chen, D. J., Gray, J. W., & Chen, F. (2010). Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities. Oncology Reports, 23(4), 1021-1026. https://doi.org/10.3892/or-00000728