Interferon-alpha repressed telomerase along with G1-accumulation of Daudi cells.
The implications of telomerase on senescence and human carcinogenesis are widely accepted, but the changes of telomerase activity along with cell cycle modulation by anticancer treatment still remain obscure. In this paper, we issued whether the telomerase activity fluctuated along with cell cycle of cultured cancer cells using the antiproliferative effect of interferon-alpha (IFN-alpha). Daudi Burkitt lymphoma cells, treated with IFN-alpha, showed proliferation inhibition and cell cycle arrest at G1. The telomerase activity at 72 h was repressed to about 20% of control cells. Furthermore, after 72 h IFN-alpha treatment, the cells in G1 phase showed the marked decrease of telomerase activity, while cells in S and G2/M still possessed it. Among expressions of telomerase-related genes, only the catalytic subunit of telomerase (hTERT) decreased from 48 h, while the template RNA component (hTERC) and telomerase-associated protein 1 (TEP-1) were not affected. The downregulation of c-Myc preceded the change of hTERT. Moreover, the analysis of cells treated with IFN-alpha for 24 h revealed that cells in G1-to-S transition mainly expressed high hTERT, while S and G2/M cells had higher level of telomerase activity than that of G1 cells. These results indicate that (i) the expression of hTERT precedes the telomerase activity which is higher in S and G2/M phases than G1 phase, (ii) IFN-alpha repressed the telomerase activity in a cell cycle-dependent manner with the downregulation of hTERT.
Akiyama
M
M
Department of Pediatrics, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan.
Iwase
S
S
Horiguchi-Yamada
J
J
Saito
S
S
Furukawa
Y
Y
Yamada
O
O
Mizoguchi
H
H
Ohno
T
T
Yamada
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D019098:Telomerase