Interferon-beta induces S phase accumulation selectively in human transformed cells.
Interferons (IFNs) generally have been characterized as antiproliferative cytokines. The cell cycle arrest in G1/G0 phase induced by type I IFNs, especially IFN-alpha, was recognized as a manifestation of their antiproliferative effects. In this article, we report that the cell cycle block in G1/G0 is observed mainly in certain cell types, such as Daudi Burkitt's lymphoma cells. In a variety of human transformed cells, but not nontransformed primary cells, IFN-beta and IFN-alpha induced a significant increase in the S phase population. The increase appeared to be due to a continued S phase entry and subsequently a failure of S phase cells to transit efficiently into G2 and M phases. The ability of tumor cells to exhibit the S phase effect correlated with proper IFN signaling and loss or inactivation of the normal G1 checkpoint conferred by the retinoblastoma protein (pRB). Overriding the G1 checkpoint switched human nontransformed primary cells from nonresponsive to sensitive to the IFN-induced effect. Therefore, the cell cycle regulatory machinery could function, at least in part, as a determining factor that affects the IFN-induced cell cycle effect. The IFN effect in transformed cells may suggest intriguing prospects for combinatorial therapies for cancer.
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Biogen, Inc., Cambridge, MA, USA.
Runkel
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Deck
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DeDios
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Barsoum
J
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D002453:Cell Cycle / Q000187:drug effects; D002461:Cell Line, Transformed / Q000166:cytology / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000502:physiology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000187:drug effects / Q000502:physiology; D016196:S Phase / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D016899:Interferon-beta