人类APOBEC3B在体内促进瘤发育,包括特征突变和转移
Cameron Durfee1, Nuri Alpay Temiz2, Rena Levin-Klein3
1Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Cell reports. Medicine
|October 5, 2023
概括
DNA 脱氨酶 APOBEC3B 在小鼠中引起癌症突变. 这项研究表明,APOBEC3B在体内驱动瘤启动,进化,异质性和转移.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 酶APOBEC3B (一种DNA细胞氨酸脱氨酶) 与各种癌症的突变有关.
- 在活体中 (in vivo) APOBEC3B与癌症发展之间的直接因果关系仍然未被证明.
研究的目的:
- 在体内建立APOBEC3B和癌症发展之间的因果关系.
- 研究APOBEC3B在瘤发病,进化和转移中的作用.
主要方法:
- 开发一种表达人类APOBEC3B瘤样水平的小鼠模型.
- 对动物发育,生育和致癌率的观察.
- 对瘤突变 (C-to-T替代,indels,结构变异) 和APOBEC3B活动的分析.
主要成果:
- 表达APOBEC3B的小鼠表现出正常发育,但成年雄性有不孕症.
- 年龄较大的表达APOBEC3B的小鼠表现出加速的致癌,瘤异质性和转移.
- 瘤在TC部位表现出增加的C-to-T突变,与APOBEC3B活性一致,并与内部和结构变异相关.
- 对于所有观察到的表型来说,APOBEC3B的催化活性是至关重要的.
结论:
- 这项研究提供了第一个体内证据,即人类APOBEC3B可以驱动瘤的开始和进展.
- APOBEC3B的活动与突变率的增加,瘤异质性和转移直接相关.
- 开发的小鼠模型是研究APOBEC3B在癌症中的作用的宝贵工具.
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