Tiwari R K, Osborne M P
Breast Cancer Research Laboratory, Memorial Sloan Kettering Cancer Center, New York, N.Y. 10021.
Cancer Lett. 1991 Jul 26;59(1):31-6. doi: 10.1016/0304-3835(91)90132-2.
The biological activity of interferons (IFNs) is presumed to be mediated through the induction of a number of IFN-inducible genes. IFN-mediated gene induction was examined in two human breast cancer cell lines, MCF-7 and BT-20. Both these cell lines were remarkably responsive to IFNs as a number of IFN inducible genes were rapidly induced. We examined the sensitivity of these genes towards 2-aminopurine (2-AP), a known inhibitor of double-stranded (ds) RNA dependent protein kinase. 2-AP has also been reported to inhibit the induction of IFN-beta 1 in response to dsRNA and the genes c-myc and c-fos in fibroblasts. In both MCF-7 and BT-20 cell lines, 2-AP selectively inhibited the IFN-induced gene responses. 2-AP did not affect levels of the oncogene, HER-2/neu. Tamoxifen (TAM), an antiestrogenic drug, which is known to inhibit the activity of protein kinase C at high concentrations, did not affect IFN-mediated gene induction. Our data is consistent with the concept that the 2-AP sensitive kinase is primarily associated with the IFN-induced gene systems and that positive and negative growth regulating stimuli in breast cancer may require the participation of distinct kinases.
干扰素（IFN）的生物活性被推测是通过诱导多种IFN诱导基因来介导的。在两种人乳腺癌细胞系MCF-7和BT-20中检测了IFN介导的基因诱导情况。这两种细胞系对IFN都有显著反应，因为许多IFN诱导基因被迅速诱导。我们检测了这些基因对2-氨基嘌呤（2-AP）的敏感性，2-AP是一种已知的双链（ds）RNA依赖性蛋白激酶抑制剂。据报道，2-AP还能抑制成纤维细胞中对dsRNA的IFN-β1诱导以及c-myc和c-fos基因。在MCF-7和BT-20细胞系中，2-AP均选择性地抑制了IFN诱导的基因反应。2-AP不影响癌基因HER-2/neu的水平。他莫昔芬（TAM）是一种抗雌激素药物，已知在高浓度时能抑制蛋白激酶C的活性，但它不影响IFN介导的基因诱导。我们的数据与以下概念一致，即2-AP敏感激酶主要与IFN诱导的基因系统相关，并且乳腺癌中正负生长调节刺激可能需要不同激酶的参与。
