Two possible mechanisms of epithelial to mesenchymal transition in invasive ductal breast cancer
Two possible mechanisms of epithelial to mesenchymal transition in invasive ductal breast cancer
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DOI：
10.1007/s10585-011-9412-x
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发表时间：
2011-12-01
影响因子：
4
通讯作者：
Katz, Elad
中科院分区：
文献类型：
--
作者：
Dubois-Marshall, Sylvie;Thomas, Jeremy S.;Katz, Elad
上皮细胞向间质细胞转化（EMT）发生在胚胎发生和正常发育中。它主要在体外和动物研究中描述，但EMT也与许多癌症的进展有关，在侵袭，转移和耐药性方面发挥作用。它与上皮特异性蛋白表达的丧失和间充质蛋白的上调密切相关，但其执行涉及几种途径。我们探讨了EMT蛋白在人类乳腺癌中的表达模式。我们询问了两个独立的高级别浸润性导管乳腺癌富集队列。我们使用定量免疫荧光来研究关键EMT蛋白的表达。定义蛋白质谱的统计学关联基于Pearson相关性。乳腺癌中E-钙粘蛋白的下调与β-连环蛋白的下调相关，但与间充质标志物的上调无关。虽然EMT相关的转录抑制因子在一些乳腺癌中表达，但它们的表达与E-钙粘蛋白不呈负相关。相反，一个额外的EMT配置文件被确定，组成蜗牛和鼻涕虫。总之，EMT在人类乳腺癌中的发生方式与体外观察到的方式不同。某些EMT事件与E-cadherin下调无关，可能构成一种新的EMT特征，值得进一步探索。
Epithelial to mesenchymal transition (EMT) occurs in embryogenesis and normal development. It has been predominantly described in vitro and in animal studies, but EMT is also implicated in the progression of many cancers with proposed roles in invasion, metastasis and resistance to treatment. It is closely associated with loss of epithelial-specific protein expression and up-regulation of mesenchymal proteins, but several pathways are implicated in its execution. We explored what are the expression patterns of EMT proteins in human breast cancer. We interrogated two independent cohorts enriched for high-grade, invasive, ductal breast cancers. We used quantitative immunofluorescence to study the expression of key EMT proteins. Statistical associations to define protein profiles were based on Pearson's correlations. E-cadherin down-regulation in breast cancer was associated with beta-catenin down-regulation, but not with up-regulation of mesenchymal markers. While EMT-related transcription repressors were expressed in some breast cancers, their expression did not negatively correlate with E-cadherin. Instead, an additional EMT profile was identified, composing Snail and Slug. In conclusion, EMT occurs in human breast cancer in a manner distinct to that seen in vitro. Certain EMT events are uncoupled from E-cadherin down-regulation and may constitute a novel EMT profile, which warrants further exploration.