Survivin may enhance DNA double-strand break repair capability by up-regulating Ku70 in human KB cells

Anticancer Res. 2009 Jan;29(1):223-8.

Abstract

Background: Survivin, expressed in almost all types of human malignancies, functions as a key factor in radioresistance primarily by inhibiting apoptosis. This study was conducted to investigate whether survivin plays a role in the DNA repair process in the KB human squamous cell carcinoma cell line.

Materials and methods: A stable KB cell line overexpressing survivin was established through the use of pIRES2-EGFP vector containing the coding region of survivin. Cells were then irradiated with X-rays and evaluated for DNA double-strand breaks (DSBs) by comet assay and flow cytometry for phospho-histone gammaH2AX. The protein levels of some DSB repair genes were detected by Western blotting analysis.

Results: Comet assay and flow cytometry for phospho-histone gammaH2AX showed that overexpression of survivin resulted in significantly fewer DSBs in irradiated cells. Among the DSB repair genes detected, the protein level of Ku70 was up-regulated in survivin-overexpressing KB cells.

Conclusion: This finding suggests that survivin may enhance DSB repair capability in KB cells by up-regulating Ku70.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Nuclear / biosynthesis*
  • Antigens, Nuclear / genetics
  • Apoptosis / genetics
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Comet Assay
  • DNA Breaks, Double-Stranded*
  • DNA Repair / physiology*
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Histones / biosynthesis
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins
  • KB Cells
  • Ku Autoantigen
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology*
  • Phosphoproteins / metabolism
  • Survivin
  • Transfection
  • Up-Regulation

Substances

  • Antigens, Nuclear
  • BIRC5 protein, human
  • DNA-Binding Proteins
  • H2AX protein, human
  • Histones
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Phosphoproteins
  • Survivin
  • Xrcc6 protein, human
  • Ku Autoantigen