APOBEC3B 是乳腺癌突变的一个酶源
Michael B Burns1, Lela Lackey, Michael A Carpenter
1Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Nature
|February 8, 2013
概括
在乳腺癌中,DNA细胞因子除氨酶APOBEC3B会导致C-to-T突变. 这种酶是这种酶.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 癌症的发展涉及多种突变,C-T转变主导乳腺癌基因组.
- 这些突变通常发生在非甲基化细胞蛋白中,并且可以聚集在一起.
研究的目的:
- 为了确定乳腺癌中C-to-T突变的来源.
- 研究APOBEC3B在乳腺癌突变和演变中的作用.
主要方法:
- 在乳腺瘤和细胞系中分析APOBEC3B信使RNA和蛋白质水平.
- 在APOBEC3B.B.的淘汰和过度表达实验中.
- 测量基因组 uracil 水平,突变频率和特定突变类型 (C-T).
- 对DNA损伤标记物 (γ-H2AX) 和细胞周期影响的评估.
主要成果:
- 在大多数乳腺瘤和细胞系中,APOBEC3B信使RNA被上调.
- 高APOBEC3B表达与突变负载增加和TP53突变相关.
- 内源APOBEC3B是乳腺癌细胞中DNAC-to-U编辑活动的主要来源.
- APOBEC3B的活动导致基因组 uracil 的增加,更高的突变频率和 C-to-T 过渡.
- 过度表达APOBEC3B会导致DNA损伤,细胞循环停止和C-T突变.
结论:
- APOBEC3B是乳腺癌中观察到的主导C-to-T突变的可能来源.
- APOBEC3B驱动的DNA去胺可能会促进TP53的失活,并有助于瘤的进化和异质性.
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