RRC ID 68574
Author Akiyama M, Yamada O, Kanda N, Akita S, Kawano T, Ohno T, Mizoguchi H, Eto Y, Anderson KC, Yamada H.
Title 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.
Journal Cancer Lett
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.
Volume 178(2)
Pages 187-97
Published 2002-4-25
DOI 10.1016/s0304-3835(01)00838-2
PII S0304383501008382
PMID 11867204
MeSH 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
IF 7.36
Human and Animal Cells K562(RCB0027)