Selective inhibition of telomerase activity during terminal differentiation of immortal cell lines.
Telomerase, the enzyme that maintains the ends of linear eukaryotic chromosomes, is active in human germ cells and in a majority of tumor tissues and immortalized cell lines. In contrast, most mature somatic cells and tissues contain low or undetectable telomerase activity, implying a stringent negative regulatory control mechanism. We report here that telomerase activity is dramatically inhibited during the terminal differentiation of HL-60 human promyelocytic leukemia cells to monocytic and granulocytic lineages. A loss of telomerase activity was seen in response to three different inducers of differentiation, was independent of differentiation-induced apoptosis, and occurred in the presence of unaltered expression of the RNA component of telomerase. Reduction in telomerase activity was also observed during the differentiation of murine F9 teratocarcinoma and C2C12 myoblast cells. In contrast, induced differentiation of murine p19 embryonal carcinoma and Neuro 2a neuroblastoma cells did not result in a loss of telomerase activity. These results are therefore consistent with the absence of telomerase activity in human somatic cells and the presence of telomerase activity in many somatic murine cells and tissues.
Bestilny
L J
LJ
Department of Medical Biochemistry, University of Calgary, Alberta, Canada.
Brown
C B
CB
Miura
Y
Y
Robertson
L D
LD
Riabowol
K T
KT
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004247:DNA / Q000032:analysis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D019098:Telomerase / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D014212:Tretinoin; D004247:DNA; D019098:Telomerase; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide