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Interferon-alpha repressed telomerase along with G1-accumulation of Daudi cells
M Akiyama1, S Iwase, J Horiguchi-Yamada
1Department of Pediatrics, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan.
Abstract:
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.
Insights
Interferon-alpha (IFN-alpha) represses cancer cell telomerase activity in a cell cycle-dependent manner. This occurs through downregulation of the human telomerase reverse transcriptase (hTERT) gene, impacting cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Telomerase activity is crucial for cellular senescence and human carcinogenesis.
- The interplay between telomerase activity, cell cycle, and anticancer treatments remains incompletely understood.
Purpose of the Study:
- To investigate the cell cycle-dependent modulation of telomerase activity by interferon-alpha (IFN-alpha) in cultured cancer cells.
- To elucidate the role of human telomerase reverse transcriptase (hTERT) in this process.
Main Methods:
- Daudi Burkitt lymphoma cells were treated with IFN-alpha.
- Cell proliferation, cell cycle distribution, and telomerase activity were assessed.
- Expression levels of telomerase-related genes (hTERT, hTERC, TEP-1) and c-Myc were analyzed.
Main Results:
- IFN-alpha induced G1 cell cycle arrest and inhibited proliferation.
- Telomerase activity was significantly repressed, particularly in G1 phase cells after 72h treatment.
- hTERT expression decreased from 48h, preceding the repression of telomerase activity, while hTERC and TEP-1 remained unaffected.
- c-Myc downregulation preceded hTERT changes.
- hTERT expression was high during G1-to-S transition, and telomerase activity was higher in S and G2/M phases compared to G1 phase.
Conclusions:
- Telomerase activity is cell cycle-dependent, with higher activity observed in S and G2/M phases compared to G1.
- IFN-alpha exerts its anticancer effect by repressing telomerase activity in a cell cycle-dependent manner, primarily through hTERT downregulation.