The MAPKERK-1,2 pathway integrates distinct and antagonistic signals from TGFα and FGF7 in morphogenesis of mouse mammary epithelium
The MAPKERK-1,2 pathway integrates distinct and antagonistic signals from TGFα and FGF7 in morphogenesis of mouse mammary epithelium
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DOI：
10.1016/j.ydbio.2007.03.013
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发表时间：
2007-06-01
影响因子：
2.7
通讯作者：
Bissell, Mina J.
中科院分区：
文献类型：
--
作者：
Fata, Jimmie E.;Mori, Hidetoshi;Bissell, Mina J.
转化生长因子-α（TGF α）和成纤维细胞生长因子-7（FGF 7）在乳腺中表现出不同的表达模式。这两种因子通过丝裂原活化激酶/细胞外调节激酶-1，2（MAPK（ERK 1，2））发出信号;然而，尚未研究它们对乳腺形态发生的独特和/或组合贡献。在离体乳腺外植体，我们表明，持续激活MAPK（ERK 1，2）1小时，诱导TGF α，是必要的，足以启动分支形态发生，而瞬时激活（15分钟）的MAPK（ERK 1，2），诱导FGF 7，导致生长无分支。与TGF α不同，FGF 7促进角蛋白-6表达细胞的持续增殖以及异位定位和增加。外植体对FGF 10的反应与对FGF 7的反应相似。FGF 7和TGF α的同时刺激表明，FGF 7诱导的MAPK（ERK 1，2）信号传导和相关表型占主导地位：FGF 7可能通过抑制两种必要的TGF α诱导的形态发生效应因子，基质金属蛋白酶-3（MMP-3/基质溶解素-1）和纤连蛋白来防止分支。我们的研究结果表明，在乳腺类器官形态发生的形态发生效应，增殖和细胞类型的决定的表达是密切依赖于MAPK（ERK 1，2）激活的激活持续时间。(C)2007年由Elsevier Inc.出版
Transforming growth factor-a (TGF alpha) and fibroblast growth factor-7 (FGF7) exhibit distinct expression patterns in the mammary gland. Both factors signal through mitogen-activated kinase/extracellular regulated kinase-1,2 (MAPK(ERK1,2)); however, their unique and/or combined contributions to mammary morphogenesis have not been examined. In ex vivo mammary explants, we show that a sustained activation of MAPK(ERK1,2) for 1 h, induced by TGF alpha, was necessary and sufficient to initiate branching morphogenesis, whereas a transient activation (15 min) of MAPK(ERK1,2), induced by FGF7, led to growth without branching. Unlike TGF alpha, FGF7 promoted sustained proliferation as well as ectopic localization of, and increase in, keratin-6 expressing cells. The response of the explants to FGF10 was similar to that to FGF7. Simultaneous stimulation by FGF7 and TGF alpha indicated that the FGF7-induced MAPK(ERK1,2) signaling and associated phenotypes were dominant: FGF7 may prevent branching by suppression of two necessary TGF alpha-induced morphogenetic effectors, matrix metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK(ERK1,2) activation. (C) 2007 Published by Elsevier Inc.