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Disorders of Erythrocytes
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依赖SMAD4的屏障限制了前列腺癌的生长和转移性进展
Zhihu Ding1, Chang-Jiun Wu, Gerald C Chu
1Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|February 4, 2011
概括
在小鼠前列腺瘤中禁用SMAD4加速了进展和转移. 包括PTEN和SMAD4在内的四个基因签名预测了人类前列腺癌的复发和致命转移.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 前列腺癌 (PCA) 管理受到异质性和对进展驱动因素的不充分理解的阻碍.
- 鼠标模型对于研究控制PCA进展的遗传元素至关重要.
研究的目的:
- 为了测试抑制进展的途径是否在惰的Pten-null小鼠前列腺瘤中被激活.
- 确定在小鼠中禁用进展障碍是否会导致转移.
主要方法:
- 对正常与Pten-null前列腺上皮的比较转录和途径分析.
- 在Pten-null小鼠中Smad4的遗传删除.
- 新兴瘤的病理学,分子和转录学分析.
主要成果:
- 在Pten-null前列腺癌中,TGFβ/BMP-SMAD4信号轴的强烈激活.
- 在Pten-null小鼠中Smad4的遗传删除导致具有100%透性的侵入性,转移性和致命的PCA.
- 细胞增殖和侵入被确定为转移性Smad4/Pten-null PCA模型中的关键特征,由环素D1和SPP1.1介导.
结论:
- 在小鼠和人类中,SMAD4是PCA进展的关键调节者.
- 一个四个基因签名 (PTEN,SMAD4,cyclin D1,SPP1) 是PSA复发和人类PCA致命转移的预后.
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