雄激素调节Bcl-2细胞死亡 (BAD) 激动剂在乳腺癌细胞中的表达和功能
Catia Morelli1,2, Chiara Chiodo2, Marta Claudia Nocito1
1Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
International journal of molecular sciences
|September 9, 2023
概括
在雌激素受体阳性乳腺癌 (ER+BC) 中,雄激素受体 (AR) 激活可对BAD蛋白进行上调. 这增强了ARAR.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 雌激素受体阳性乳腺癌 (ER+BC) 是乳腺癌的主要亚型.
- 在ER+BC中的雄激素受体 (AR) 表达与更好的结果和减少的增殖有关.
- 众所周知,雄激素可以抵消正常乳腺上皮和ER+BC模型中的增殖.
研究的目的:
- 阐明AR在ER+BC中的保护作用.
- 通过确定雄激素施加抗生殖效应的新机制.
- 研究Bcl-2-家族蛋白BAD在AR信号传递中的作用.
主要方法:
- 对癌症基因组图谱 (TCGA) 数据库对ER+BC.中BAD表达的分析.
- 研究AR和BAD蛋白相互作用和细胞局部化.
- 评估AR和BAD对目标基因 (如环林D1.1) 的促进子区域 (AP-1,ARE) 的招募.
- 在对雄激素刺激的反应中评估线粒体功能.
主要成果:
- 在ER+BC中,AR激活调高了BAD的表达.
- 在ER+BC患者中,BAD表达与改善无病生存率相关.
- 接体激活的AR影响了BAD.的核和线粒体定位.
- 核BAD和AR相互作用,并被招募到环素D1促进体,抑制扩散.
- 线粒体丰富BAD和AR与线粒体功能下降有关.
结论:
- 雄激素通过涉及BAD的新机制在ER+BC中发挥保护作用.
- 雄激素调节BAD表达,局部化,并作为细胞循环抑制剂起作用.
- 这一途径增强了ER+BC中雄激素信号传递的抗增殖和保护作用.
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