夏普
生物
Fas配体
干扰素调节因子
细胞凋亡
癌症研究
干扰素
凋亡抑制因子
激酶
程序性细胞死亡
细胞生物学
免疫学
半胱氨酸蛋白酶
免疫系统
先天免疫系统
遗传学
作者
Mamta Chawla‐Sarkar,Daniel J. Lindner,Liu Yf,Bryan R.G. Williams,Ganes C. Sen,Robert H. Silverman,Ernest C. Borden
出处
期刊:Apoptosis
[Springer Nature]
日期:2003-01-01
卷期号:8 (3): 237-249
被引量:761
标识
DOI:10.1023/a:1023668705040
摘要
IFNs are a family of cytokines with pleiotropic biological effects mediated by scores of responsive genes. IFNs were the first human proteins to be effective in cancer therapy and were among the first recombinant DNA products to be used clinically. Both quality and quantity of life has been improved in response to IFNs in various malignancies. Despite its beneficial effects, unraveling the mechanisms of the anti-tumor effects of IFN has proven to be a complex task. IFNs may mediate anti-tumor effects either indirectly by modulating immunomodulatory and anti-angiogenic responses or by directly affecting proliferation or cellular differentiation of tumor cells. Both direct or indirect effects of IFNs result from induction of a subset of genes, called IFN stimulated genes (ISGs). In addition to the ISGs implicated in anti-viral, anti-angiogenic, immunomodulatory and cell cycle inhibitory effects, oligonucleotide microarray studies have identified ISGs with apoptotic functions. These include TNF-α related apoptosis inducing ligand (TRAIL/Apo2L), Fas/FasL, XIAP associated factor-1 (XAF-1), caspase-4, caspase-8, dsRNA activated protein kinase (PKR), 2'5'A oligoadenylate synthetase (OAS), death activating protein kinases (DAP kinase), phospholipid scramblase, galectin 9, IFN regulatory factors (IRFs), promyelocytic leukemia gene (PML) and regulators of IFN induced death (RIDs). In vitro IFN-α, IFN-β and IFN-γ induced apoptosis in multiple cell lines of varied histologies. This review will emphasize possible mechanisms and the role of ISGs involved in mediating apoptotic function of IFNs.
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