Marusawa Hiroyuki
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Int J Biochem Cell Biol. 2008;40(8):1399-402. doi: 10.1016/j.biocel.2008.01.018. Epub 2008 Jan 25.
Cancer develops via a multistep process that occurs through the accumulation of somatic mutations of tumor-related genes that govern cell proliferation, regeneration, and apoptosis. The question how normal cells acquire the genetic changes that lead to malignant transformation is, however, unknown at present. Activation-induced cytidine deaminase (AID) produces immune-diversity by inducing somatic hypermutations and class-switch recombinations in human immunoglobulin genes. Unfortunately, this function of AID as a genome mutator could aim at the generation of somatic mutations in various host genes of non-lymphoid tissues and contribute to tumorgenesis. Notably, aberrant AID expression can be triggered by several pathogenic factors, including Helicobacter pylori infection and proinflammatory cytokine stimulation, in human epithelial cells, whereas AID expression is absent in those cells under physiologic conditions. Thus, aberrant AID activity in epithelial tissues may provide the critical link between inflammation, somatic mutations, and cancer development.
癌症是通过一个多步骤过程发展而来的，该过程是通过控制细胞增殖、再生和凋亡的肿瘤相关基因的体细胞突变积累而发生的。然而，目前尚不清楚正常细胞是如何获得导致恶性转化的基因变化的。激活诱导的胞苷脱氨酶（AID）通过诱导人类免疫球蛋白基因中的体细胞超突变和类别转换重组产生免疫多样性。不幸的是，AID作为基因组突变体的这一功能可能旨在在非淋巴组织的各种宿主基因中产生体细胞突变，并促进肿瘤发生。值得注意的是，在人类上皮细胞中，包括幽门螺杆菌感染和促炎细胞因子刺激在内的几种致病因素可触发AID的异常表达，而在生理条件下这些细胞中不存在AID表达。因此，上皮组织中异常的AID活性可能是炎症、体细胞突变和癌症发展之间的关键联系。
