期刊
CELLULAR SIGNALLING
卷 24, 期 4, 页码 961-968出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2011.12.019
关键词
Mitotic checkpoint; Transforming Growth Factor-beta (TGF-beta); Bone morphogenetic proteins (BMPs); Breast cancer
类别
资金
- National Natural Science Foundation of China [30971451, 90919028, 31171432, 31071306]
- MOST [2010CB945000, 2010CB944900, 2011CB965100, 2011CBA01106]
- Science and Technology Commission of Shanghai Municipality [09DZ2260100, 11ZR1438500, 11XD1405300]
Aberrant expression of mitotic checkpoint genes compromises mitotic checkpoint, leads to chromosome instability and tumorigenesis. However, the cell signals that control mitotic checkpoint gene expression have not been reported so far. In the present study we show that, in human breast cancer cells, chemical inhibition of Bone morphogenetic proteins (BMPs), but not Transforming Growth Factor-beta (TGF-beta), abrogates the mitotic arrest induced by nocodazole. Protein expression analysis reveals that inhibition of BMP signaling dramatically down regulates protein levels of mitotic checkpoint components BUB3, Hec1, TTK and MAD2, but inhibition of TGF-beta has relatively minor effect on the expression of these proteins. Activation of BMP signaling specifically up regulates BUB3, and activation of Activin A signaling globally down regulates these proteins level. Furthermore, overexpressing MAD2, TTK, BUB3 or Hec1 significantly rescues the mitotic arrest defect caused by BMP inhibition. Our results demonstrated for the first time that TGF-beta family cytokines are cellular signals regulating mitotic checkpoint and perturbations in intrinsic BMP signaling could lead to suppression of mitotic checkpoint signaling by downregulating key checkpoint proteins. The results suggest a possible mechanism by which dysregulation of TGF-beta signaling causes mitotic checkpoint defects and drives tumorigenesis. The finding also provides a potential and more specific strategy for cancer prevention by targeting BMP and mitotic checkpoint connection. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据