C/EBPβ at the core of the TGFβ cytostatic response and its evasion in metastatic breast cancer cells
C/EBPβ at the core of the TGFβ cytostatic response and its evasion in metastatic breast cancer cells
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DOI：
10.1016/j.ccr.2006.07.019
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发表时间：
2006-09-01
期刊：
影响因子：
50.3
通讯作者：
Massague, Joan
中科院分区：
文献类型：
--
作者：
Gomis, Roger R.;Alarcon, Claudio;Massague, Joan
乳腺癌可能通过积累未知性质的缺陷来逃避TGFO的生长抑制作用，这些缺陷选择性地消除细胞抑制基因反应。我们发现，转录因子C/EBPO是必不可少的TGFO诱导细胞周期抑制剂p151 NK 4 b的FoxO-Smad复合物和阻遏c-MYC的E2 F4/5-Smad复合物在人类上皮细胞。这些细胞抑制反应在我们测试的一半患者的转移性乳腺癌细胞中选择性缺失。这种损失的基础被追溯到过量的C/EBPO抑制亚型LIP。我们认为，C/EBPO在协调TGFO细胞抑制基因反应中起着关键作用，其功能障碍可能会引发乳腺癌逃避这些反应。
Breast cancers may evade the growth-inhibitory action of TGFO by accumulating defects of unknown nature that selectively eliminate cytostatic gene responses. We found the transcription factor C/EBPO to be essential for TGFO induction of the cell cycle inhibitor p151NK4b by a FoxO-Smad complex and repression of c-MYC by an E2F4/5-Smad complex in human epithelial cells. These cytostatic responses are selectively missing in metastatic breast cancer cells from half of the patients that we tested. The basis for this loss was traced to an excess of the C/EBPO inhibitory isoform LIP. We suggest that C/EBPO plays a key role in the coordination of TGFO cytostatic gene responses, and its malfunction may trigger evasion of these responses in breast cancer.