From the Division of Hematology-Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611 and.
J Biol Chem. 2013 Nov 15;288(46):33006-15. doi: 10.1074/jbc.M113.460741. Epub 2013 Oct 2.
There is emerging evidence that the IFN-inducible family of Slfn genes and proteins play important roles in cell cycle progression and control of cellular proliferation, but the precise functional roles of different Slfn members in the regulation of tumorigenesis remain unclear. In the present study, we undertook a systematic analysis on the expression and functional relevance of different mouse Slfn genes in malignant melanoma and renal cell carcinoma cells. Our studies demonstrate that several mouse Slfn genes are up-regulated in response to IFN treatment of mouse melanoma and renal cell carcinoma cells, including Slfn1, Slfn2, Slfn4, Slfn5, and Slfn8. Our data show that Slfn2 and Slfn3 play essential roles in the control of mouse malignant melanoma cell proliferation and/or anchorage-independent growth, suggesting key and non-overlapping roles for these genes in the control of malignant melanoma tumorigenesis. In renal cell carcinoma cells, in addition to Slfn2 and Slfn3, Slfn5 also exhibits important antineoplastic effects. Altogether, our findings indicate important functions for distinct mouse Slfn genes in the control of tumorigenesis and provide evidence for differential involvement of distinct members of this gene family in controlling tumorigenesis. They also raise the potential of future therapeutic approaches involving modulation of expression of members of this family of genes in malignant melanoma and renal cell carcinoma.
有新的证据表明，IFN 诱导的 Slfn 基因家族和蛋白质在细胞周期进程和细胞增殖控制中发挥重要作用，但不同 Slfn 成员在肿瘤发生调节中的精确功能作用仍不清楚。在本研究中，我们对不同的小鼠 Slfn 基因在恶性黑色素瘤和肾细胞癌细胞中的表达和功能相关性进行了系统分析。我们的研究表明，几种小鼠 Slfn 基因在 IFN 处理小鼠黑色素瘤和肾细胞癌细胞时上调，包括 Slfn1、Slfn2、Slfn4、Slfn5 和 Slfn8。我们的数据表明，Slfn2 和 Slfn3 在控制小鼠恶性黑色素瘤细胞增殖和/或非锚定依赖性生长中起重要作用，表明这些基因在控制恶性黑色素瘤肿瘤发生中具有关键且不重叠的作用。在肾细胞癌细胞中，除了 Slfn2 和 Slfn3 之外，Slfn5 还表现出重要的抗肿瘤作用。总之，我们的发现表明不同的小鼠 Slfn 基因在肿瘤发生控制中具有重要功能，并为该基因家族的不同成员在控制肿瘤发生中的不同参与提供了证据。它们还提出了未来涉及调节恶性黑色素瘤和肾细胞癌中该基因家族成员表达的治疗方法的潜力。
