Chatterjee D, Savarese T M
Division of Biology and Medicine, Brown University, Providence, RI 02912.
Cancer Chemother Pharmacol. 1992;30(1):12-20. doi: 10.1007/BF00686479.
Recombinant human interferon-beta ser17 (IFN-beta ser17), a cytokine that exhibits both antiviral and antiproliferative activity against a wide variety of cell types, causes a time- and dose-dependent inhibition of monolayer growth and of the expression of the c-myc proto-oncogene in DLD-1 Clone A human colon-carcinoma cells. The suppression of c-myc expression mediated by IFN-beta ser17 is due to a posttranscriptional destabilization of c-myc mRNA rather than to an inhibition of c-myc mRNA transcription. There is evidence suggesting that the selective reduction in the half-life of c-myc mRNA in IFN-beta ser17-treated cells occurs through an increase in the activity of the 2',5'-oligoadenylate synthetase/RNase L [2',5'-oligo (A) synthetase] pathway in DLD-1 Clone A cells. Cotreatment of these cells with IFN-beta ser17 and the anticancer agent N-methylformamide leads to the partial abrogation of 2',5'-oligo (A) synthetase activity and the stabilization of c-myc mRNA. These findings suggest that there is a correlation between the IFN-beta ser17-mediated suppression of c-myc expression and the induction of 2',5'-oligo (A) synthetase activity in DLD-1 clone A cells.
重组人干扰素-β17（IFN-β17）是一种对多种细胞类型均具有抗病毒和抗增殖活性的细胞因子，它能对人结肠癌DLD-1克隆A细胞的单层生长以及c-myc原癌基因的表达产生时间和剂量依赖性抑制。IFN-β17介导的c-myc表达抑制是由于c-myc mRNA的转录后不稳定，而非c-myc mRNA转录受到抑制。有证据表明，在经IFN-β17处理的细胞中，c-myc mRNA半衰期的选择性缩短是通过DLD-1克隆A细胞中2',5'-寡腺苷酸合成酶/RNase L[2',5'-寡聚（A）合成酶]途径活性的增加而发生的。用IFN-β17和抗癌剂N-甲基甲酰胺共同处理这些细胞会导致2',5'-寡聚（A）合成酶活性部分消除以及c-myc mRNA稳定。这些发现表明，在DLD-1克隆A细胞中，IFN-β17介导的c-myc表达抑制与2',5'-寡聚（A）合成酶活性的诱导之间存在相关性。
