Organization of mammary epithelial cells into 3D acinar structures requires glucocorticoid and JNK signaling.
Organization of mammary epithelial cells into 3D acinar structures requires glucocorticoid and JNK signaling.
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DOI：
10.1083/jcb.200403020
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发表时间：
2004-07-05
期刊：
影响因子：
--
通讯作者：
Martin F
中科院分区：
文献类型：
--
作者：
Murtagh J;McArdle E;Gilligan E;Thornton L;Furlong F;Martin F
在浓缩的富含层粘连蛋白的细胞外基质上培养的乳腺上皮细胞形成3D腺泡结构，其成熟为围绕管腔的极化单层。在缺乏糖皮质激素的情况下，成熟腺泡形成失败，腺泡相关激活蛋白1（AP 1）和核因子κB转录因子DNA结合谱的表达丢失。用JNK抑制剂SP 600125治疗引起类似的效果，而乳腺上皮细胞作为腺泡的正常组织以糖皮质激素依赖性方式引起JNK活化。形成的腺泡以糖皮质激素依赖的方式表达BRCA 1、GADD 45 β、MEKK 4和JNK激活复合物GADD 45β− MEKK 4。在腺泡中也检测到JNK催化的c-Jun磷酸化。此外，β4整合素的表达及其启动子被AP 1组分c-Jun和Fos原位占据是糖皮质激素依赖性的。这些结果表明，糖皮质激素信号通过JNK调节AP 1转录因子和β4整合素表达的途径调节腺泡完整性。
Mammary epithelial cells cultured on a concentrated laminin-rich extracellular matrix formed 3D acinar structures that matured to polarized monolayers surrounding a lumen. In the absence of glucocorticoids mature acinus formation failed and the expression of an acinus-associated, activator protein 1 (AP1) and nuclear factor κB transcription factor DNA-binding profile was lost. Treatment with the JNK inhibitor, SP600125, caused similar effects, whereas normal organization of the mammary epithelial cells as acini caused JNK activation in a glucocorticoid-dependent manner. The forming acini expressed BRCA1, GADD45β, MEKK4, and the JNK activating complex GADD 45β−MEKK4 in a glucocorticoid-dependent fashion. JNK catalyzed phosphorylation of c-Jun was also detected in the acini. In addition, expression of β4 integrin and in situ occupation of its promoter by AP1 components, c-Jun and Fos, was glucocorticoid dependent. These results suggest that glucocortocoid signaling regulates acinar integrity through a pathway involving JNK regulation of AP1 transcription factors and β4 integrin expression.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
DOI：
10.1083/jcb.144.6.1337
发表时间：
1999-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Farrelly N;Lee YJ;Oliver J;Dive C;Streuli CH
通讯作者：
Streuli CH
影响因子：
5.3
作者：
Mita, H;Tsutsui, J;Saito, H
通讯作者：
Saito, H
DOI：
10.1073/pnas.93.24.13595
发表时间：
1996-11-26
影响因子：
11.1
作者：
Monteiro, ANA;August, A;Hanafusa, H
通讯作者：
Hanafusa, H
影响因子：
64.8
作者：
BINETRUY, B;SMEAL, T;KARIN, M
通讯作者：
KARIN, M