Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
Eur J Immunol. 2014 Sep;44(9):2785-801. doi: 10.1002/eji.201344322.
Unless stimulated by a chronic inflammatory agent, such as mineral oil, plasma cell tumors are rare in young BALB/c mice. This raises the questions: What do inflammatory tissues provide to promote mutagenesis? And what is the nature of mutagenesis? We determined that mineral oil-induced plasmacytomas produce large amounts of endogenous retroelements--ecotropic and polytropic murine leukemia virus and intracisternal A particles. Therefore, plasmacytoma formation might occur, in part, by de novo insertion of these retroelements, induced or helped by the inflammation. We recovered up to ten de novo insertions in a single plasmacytoma, mostly in genes with common retroviral integration sites. Additional integrations accompany tumor evolution from a solid tumor through several generations in cell culture. The high frequency of de novo integrations into cancer genes suggests that endogenous retroelements are coresponsible for plasmacytoma formation and progression in BALB/c mice.
除非受到慢性炎症因子（如矿物油）的刺激，否则在年轻的 BALB/c 小鼠中，浆细胞瘤很少见。这就提出了这样的问题：炎症组织提供了什么来促进突变？突变的本质是什么？我们发现，矿物油诱导的浆细胞瘤会产生大量内源性逆转录元件——ecotropic 和 polytropic 鼠白血病病毒和核内 A 颗粒。因此，浆细胞瘤的形成可能部分是由于这些逆转录元件的新插入，这些插入是由炎症诱导或协助的。我们从单个浆细胞瘤中恢复了多达十个新的插入，主要是在具有常见逆转录病毒整合位点的基因中。在细胞培养中，从实体瘤到多个世代的肿瘤进化过程中，还会发生其他的整合。新插入癌症基因的高频度提示，内源性逆转录元件共同导致 BALB/c 小鼠浆细胞瘤的形成和进展。
