Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model.
Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model.
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DOI：
10.1083/jcb.200505098
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发表时间：
2005-11-21
期刊：
影响因子：
--
通讯作者：
Rosen JM
中科院分区：
文献类型：
--
作者：
Xian W;Schwertfeger KL;Vargo-Gogola T;Rosen JM
成纤维细胞生长因子（FGF）家族的成员和FGF受体（FGFR）已经涉及介导乳腺发育和转化的各个方面。为了阐明在模拟极化上皮细胞的背景下FGFR 1作用的分子机制，我们开发了表达药物诱导型FGFR 1（iFGFR 1）的体外三维HC 11小鼠乳腺上皮细胞培养模型。使用这种条件模型，在这些生长停滞和极化的乳腺腺泡中，iFGFR 1活化最初导致细胞增殖重新启动，腔细胞存活增加，细胞极性丧失，导致腺泡结构破坏，其特征在于不存在空腔。iFGFR 1激活还导致侵袭性的获得和基质金属蛋白酶3（MMP-3）的诱导，引起E-钙粘蛋白的切割和平滑肌肌动蛋白和波形蛋白的表达增加。添加pan MMP抑制剂可消除这些表型，但不能阻止iFGFR 1对细胞增殖或存活的影响。
Members of the fibroblast growth factor (FGF) family and the FGF receptors (FGFRs) have been implicated in mediating various aspects of mammary gland development and transformation. To elucidate the molecular mechanisms of FGFR1 action in a context that mimics polarized epithelial cells, we have developed an in vitro three-dimensional HC11 mouse mammary epithelial cell culture model expressing a drug-inducible FGFR1 (iFGFR1). Using this conditional model, iFGFR1 activation in these growth-arrested and polarized mammary acini initially led to reinitiation of cell proliferation, increased survival of luminal cells, and loss of cell polarity, resulting in the disruption of acinar structures characterized by the absence of an empty lumen. iFGFR1 activation also resulted in a gain of invasive properties and the induction of matrix metalloproteinase 3 (MMP-3), causing the cleavage of E-cadherin and increased expression of smooth muscle actin and vimentin. The addition of a pan MMP inhibitor abolished these phenotypes but did not prevent the effects of iFGFR1 on cell proliferation or survival.
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DOI：
10.1186/bcr53
发表时间：
2000
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dickson C;Spencer-Dene B;Dillon C;Fantl V
通讯作者：
Fantl V
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
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影响因子：
64.8
作者：
Radisky, DC;Levy, DD;Bissell, MJ
通讯作者：
Bissell, MJ
DOI：
10.1073/pnas.0308090100
发表时间：
2004-02-03
影响因子：
11.1
作者：
Seton-Rogers, SE;Lu, Y;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
7.8
作者：
Lochter, A;Galosy, S;Muschler, J;Freedman, N;Werb, Z;Bissell, MJ
通讯作者：
Bissell, MJ