Tiwari R K, Wong G Y, Liu J, Miller D, Osborne M P
Breast Cancer Research Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10021.
Cancer Lett. 1991 Dec 9;61(1):45-52. doi: 10.1016/0304-3835(91)90075-s.
The cytotoxic effect of a combination of interferons (type I and II) and tumor necrosis factor (TNF), with an antiestrogenic drug, tamoxifen (TAM), was investigated in the estrogen receptor positive human breast carcinoma cell line, MCF-7. Cytotoxicity was measured by the MTT assay. In an attempt to define the molecular basis for the interaction between the interferons (IFNs) and TNF or any one of the cytokines with TAM, the induction characteristics of a number of IFN-induced mRNAs in response to IFNs, TNF, and TAM were studied. We observed an augmentation of the cytotoxic effect of TNF when it was combined with TAM. There appears to be an overlap in signalling mechanisms of IFNs and TNF as two of the IFN-inducible genes, 1-8 and 6-16 are also induced by TNF. mRNA 1-8 was induced by both IFN-alpha (type I) and IFN-gamma (type II). We conclude that TNF potentiates the cytotoxic effects of TAM in MCF-7 cells and that the three cytokines IFN-alpha, IFN-gamma, and TNF share some pathways that lead to specific induction of some cytokine responsive genes.
在雌激素受体阳性的人乳腺癌细胞系MCF-7中，研究了干扰素（I型和II型）与肿瘤坏死因子（TNF）联合一种抗雌激素药物他莫昔芬（TAM）的细胞毒性作用。通过MTT法测定细胞毒性。为了确定干扰素（IFN）与TNF或任何一种细胞因子与TAM之间相互作用的分子基础，研究了多种IFN诱导的mRNA对IFN、TNF和TAM的诱导特征。我们观察到TNF与TAM联合时细胞毒性作用增强。IFN和TNF的信号传导机制似乎存在重叠，因为两个IFN诱导基因1-8和6-16也可被TNF诱导。mRNA 1-8可被I型干扰素α和II型干扰素γ诱导。我们得出结论，TNF增强了TAM对MCF-7细胞的细胞毒性作用，并且三种细胞因子IFN-α、IFN-γ和TNF共享一些导致某些细胞因子反应性基因特异性诱导的途径。
