在胚胎发育和瘤发生过程中SIRT7和p53的相互作用
Berta N Vazquez1,2, Irene Fernández-Duran1, Yurdiana Hernandez3
1Chromatin Biology Laboratory, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain.
赛尔图因7 (SIRT7) 影响胚胎发育和癌症,与瘤抑制剂p53.3相互作用. 缺少SIRT7不会通过p53导致胚胎死亡,但SIRT7损失会在p53缺乏的小鼠中加剧癌症.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 发育生物学是发展生物学.
背景情况:
- 瘤抑制剂p53调节细胞循环,DNA修复和亡.
- 赛尔图因7 (SIRT7) 是细胞应激反应的关键调节剂,其与p53在癌症中的作用尚不清楚.
- 在人类癌症中,SIRT7经常过度表达,其耗尽会导致小鼠的发育缺陷.
研究的目的:
- 研究SIRT7和p53在胚胎发育过程中的相互作用.
- 确定SIRT7在瘤发生中的作用,特别是在p53.3的背景下.
- 探索SIRT7表达在具有p53突变的人类癌症中的临床相关性.
主要方法:
- 产生SIRT7和p53双击鼠标模型.
- 在淘汰赛小鼠胚胎发育和生存的分析.
- 对SIRT7和p53相互作用的转录基因分析.
- 对SIRT7表达与人类瘤患者预后的相关性分析.
主要成果:
- 缺少SIRT7的胚胎死亡率独立于p53.
- 在p53淘汰赛小鼠中,SIRT7的哈普隆缺陷加速了瘤发生.
- 低SIRT7表达与p53突变的人类瘤的预后不佳相关.
- 发现了一种SIRT7,p53,上皮细胞转化为介质细胞转化 (EMT) 和细胞外矩阵调节之间的新联系.
结论:
- 在胚胎发育中SIRT7的作用与p53.3不同.
- 根据p53.7的背景,SIRT7可以充当瘤基因或瘤抑制剂.
- 在EMT和ECM调节中发现的SIRT7-p53相互作用为发展和癌症进展提供了新的见解.
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