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.
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.
Akiyama
Masaharu
M
Department of Pediatrics, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. masaharu@bf6.so-net.ne.jp
Yamada
Osamu
O
Kanda
Naotoshi
N
Akita
Shinobu
S
Kawano
Takeshi
T
Ohno
Tsuneya
T
Mizoguchi
Hideaki
H
Eto
Yoshikatsu
Y
Anderson
Kenneth C
KC
Yamada
Hisashi
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D016895:Culture Media, Serum-Free; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D020014:K562 Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology* / Q000528:radiation effects; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D016615:Telomere / Q000473:pathology; D014162:Transfection
D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine; D005047:Etoposide; D019098:Telomerase; D006918:Hydroxyurea