Telomerase overexpression in K562 leukemia cells protects against apoptosis by serum deprivation and double-stranded DNA break inducing agents, but not against DNA synthesis inhibitors

Cancer Lett. 2002 Apr 25;178(2):187-97. doi: 10.1016/s0304-3835(01)00838-2.

Abstract

Telomeres are specialized DNA/protein structures that act as protective caps to prevent end fusions. The maintenance of telomeres is essential for chromosomal stability. Telomerase is regulated by human telomerase reverse transcriptase (hTERT). c-Myc oncoprotein is also implicated in the positive regulation of hTERT expression. We show here that two clones of hTERT-transfected K562 erythroleukemia cells have elongated telomeres (22.5 and 24.0 kb), whereas telomere length of both c-Myc-transfected K562 cells and parental K562 cells is 6.5 kb. Telomerase activity and hTERT mRNA expression increased in hTERT-transfected K562 cells, while the expression levels of telomerase activity and hTERT in c-Myc-transfected K562 cells were similar to that in parental K562 cells, despite an overexpression of c-Myc. Importantly, we found that hTERT-transfected K562 cells are protected against apoptosis induced by serum deprivation and double-stranded DNA break inducing agents (ionizing irradiation, and etoposide (VP-16)), but not against DNA synthesis inhibitors (1-beta-D-arabinofuranosylcytosine and hydroxyurea). These findings suggest that overexpression of telomerase by transfecting hTERT confers telomere-elongation and resistance to double-stranded DNA break inducing agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptosis / radiation effects
  • Culture Media, Serum-Free
  • Cytarabine / pharmacology
  • DNA Damage / drug effects
  • DNA Damage / genetics
  • DNA Damage / radiation effects
  • DNA Replication / drug effects
  • Etoposide / pharmacology
  • Humans
  • Hydroxyurea / pharmacology
  • K562 Cells / drug effects
  • K562 Cells / enzymology*
  • K562 Cells / pathology*
  • K562 Cells / radiation effects
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Telomerase / biosynthesis*
  • Telomerase / genetics
  • Telomere / pathology
  • Transfection

Substances

  • Antineoplastic Agents
  • Culture Media, Serum-Free
  • Nucleic Acid Synthesis Inhibitors
  • Cytarabine
  • Etoposide
  • Telomerase
  • Hydroxyurea