Regulation of DNA-dependent protein kinase activity in leukemic cells

Oncogene. 1997 Nov 6;15(19):2343-8. doi: 10.1038/sj.onc.1201402.

Abstract

The DNA-dependent protein kinase (DNA-PK) complex is composed of a catalytic (DNA-PKcs), and a regulatory subunit (Ku70/Ku86 heterodimer). The expression and function of DNA-PK subunits was investigated in purified blood lymphocytes obtained from patients with chronic lymphocytic leukemia (CLL) either refractory to chemotherapy or untreated. Variations in DNA-PK activity were found amongst CLL samples by comparison to human cell lines. It was noticeable that the low DNA-PK activity was associated with samples from untreated patients that exhibited a sensitivity phenotype, determined in vitro, to the radiomimetic agent neocarcinostatin by comparison to samples from refractory patients. The regulation in DNA-PK activity was associated with Ku heterodimer expression while DNA-PKcs was unaffected. Moreover, the presence of an altered form of the Ku86 subunit was identified in samples with low DNA-PK activity. These results suggest a regulation process of the DNA-PK activity in fresh human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Extracts
  • Cell Nucleus / enzymology
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology*
  • Lymphocytes / enzymology
  • Male
  • Middle Aged
  • Nuclear Proteins
  • Protein-Serine-Threonine Kinases / metabolism*
  • Zinostatin / pharmacology

Substances

  • Cell Extracts
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Zinostatin
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein-Serine-Threonine Kinases