PI3K regulates branch initiation and extension of cultured mammary epithelia via Akt and Rac1 respectively.
PI3K regulates branch initiation and extension of cultured mammary epithelia via Akt and Rac1 respectively.
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PI3K分别通过AKT和RAC1调节培养的乳腺上皮的分支开始和扩展。
DOI：
10.1016/j.ydbio.2013.04.029
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发表时间：
2013-07-15
影响因子：
2.7
通讯作者：
Nelson, Celeste M.
中科院分区：
文献类型：
--
作者：
Zhu, Wenting;Nelson, Celeste M.
乳腺的树形结构是由分支形态发生产生的，受微环境的多种信号调控。在这里，我们使用乳腺上皮管的三维培养模型研究了PI3K的下游信号如何调节乳腺分支的不同步骤。我们发现PI3K对于分支的起始和延伸都是必需的。激活Akt在分支起始位点增强，其负调控因子PTEN被Sprouty2 （SPRY2）信号阻断；抑制Akt抑制分支起始。SPRY2的表达模式，以及Akt的激活和分支的起始，是由内源性细胞骨架收缩的机械信号控制的。相比之下，激活的gtp结合的Rac1定位于新生枝的边缘，并且是枝伸长所必需的。这些数据表明，PI3K网络整合了机械和生化信号来控制乳腺上皮细胞的分支形态发生。
The tree-like architecture of the mammary gland is generated by branching morphogenesis, which is regulated by many signals from the microenvironment. Here we examined how signaling downstream of phosphoinositide 3-kinase (PI3K) regulates different steps of mammary branching using three-dimensional culture models of the mammary epithelial duct. We found that PI3K was required for both branch initiation and elongation. Activated Akt was enhanced at branch initiation sites where its negative regulator, PTEN, was blocked by signaling via Sprouty2 (SPRY2); inhibiting Akt prevented branch initiation. The pattern of SPRY2 expression, and thus of Akt activation and branch initiation, was controlled by mechanical signaling from endogenous cytoskeletal contractility. In contrast, activated GTP-bound Rac1 localized to the leading edge of nascent branches and was required for branch elongation. These data suggest that the PI3K network integrates mechanical and biochemical signaling to control branching morphogenesis of mammary epithelial cells.
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影响因子：
21.3
作者：
Joffre, Carine;Barrow, Rachel;Kermorgant, Stephanie
通讯作者：
Kermorgant, Stephanie
影响因子：
3.7
作者：
Cernuda-Morollón E;Millán J;Shipman M;Marelli-Berg FM;Ridley AJ
通讯作者：
Ridley AJ
影响因子：
4.8
作者：
Edwin, F;Singh, R;Patel, TB
通讯作者：
Patel, TB
DOI：
10.1016/0006-291x(89)92189-x
发表时间：
1989-03-31
影响因子：
3.1
作者：
ISHIHARA, H;MARTIN, BL;HARTSHORNE, DJ
通讯作者：
HARTSHORNE, DJ
影响因子：
4.8
作者：
Chen, Connie S.;Nelson, Celeste M.;Radisky, Derek C.
通讯作者：
Radisky, Derek C.