Epithelial-to-mesenchymal transition confers resistance to apoptosis in three murine mammary epithelial cell lines
Epithelial-to-mesenchymal transition confers resistance to apoptosis in three murine mammary epithelial cell lines
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DOI：
10.1111/j.1432-0436.2006.00075.x
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发表时间：
2006-06-01
期刊：
影响因子：
2.9
通讯作者：
Watson, Christine J.
中科院分区：
文献类型：
--
作者：
Robson, Ewan J. D.;Khaled, Walid T.;Watson, Christine J.
上皮-间质转化（EMT）是胚胎发生和发育的重要过程，其特征是细胞形态改变、细胞粘附丧失和迁移能力获得。这一过程的失调与肿瘤发生有关，介导肿瘤细胞获得迁移和侵袭表型。乳腺上皮细胞提供了一个很好的模型，在其中研究的过程中，来自乳腺组织，利用EMT，以促进分支形态发生，通过它的发展腺体迁移到和入侵的脂肪垫。不适当的EMT与乳腺导管增生和乳腺肿瘤转移的进展密切相关。我们研究了三种小鼠乳腺上皮细胞系在EMT诱导后的形态学和分子变化。EpH-4和NMuMG细胞系中转化生长因子（TGF）-β 1诱导EMT，但乙醇不诱导EMT，而KIM-2细胞系对TGF-β 1部分耐药，但对乙醇完全反应。对EMT诱导试剂的反应显示出严重依赖于处理时间，融合细胞没有反应。与未处理的对照相比，延时摄影鉴定了用EMT诱导试剂预处理的细胞在伤口愈合期间的运动性增加。此外，EMT赋予抵抗UV诱导的细胞凋亡。我们的数据表明，在评估EMT时，评估表型标记物的丢失和获得以外的特征可能是有益的，并有助于证据表明，不适当的EMT有助于获得对细胞凋亡的抵抗，这是肿瘤生存所需的关键特征。
Epithelial-to-mesenchymal transition (EMT) is an essential embryogenic and developmental process, characterized by altered cellular morphology, loss of cell adhesion, and gain of migratory ability. Dysregulation of this process has been implicated in tumorigenesis, mediating the acquisition of migratory and invasive phenotypes by tumor cells. Mammary epithelial cells provide an excellent model in which to study the process, being derived from mammary gland tissue that utilizes EMT to facilitate branching morphogenesis through which the developing gland migrates into and invades the fat pad. Inappropriate EMT has been heavily implicated in the progression of ductal hyperplasia and mammary tumor metastasis. We examined the morphological and molecular changes of three murine mammary epithelial cell lines following EMT induction. EMT was induced in the EpH-4 and NMuMG cell lines by transforming growth factor (TGF)-beta 1 but not by ethanol, while the KIM-2 cell line was partially resistant to TGF-beta 1 but responded fully to ethanol. The response to EMT-inducing reagent was shown to be critically dependent on the time of treatment, with confluent cells failing to respond. Timelapse photography identified increased motility during wound healing in cells pre-treated with EMT-inducing reagent compared with untreated controls. Furthermore, EMT conferred resistance to UV-induced apoptosis. Our data indicate that evaluation of characteristics other than loss and gain of phenotypic markers may be of benefit when assessing EMT, and contribute to the evidence suggesting that inappropriate EMT facilitates the acquisition of resistance to apoptosis, a key characteristic required for tumor survival.