Expression of chicken ovalbumin upstream promoter-transcription factor II enhances invasiveness of human lung carcinoma cells
Expression of chicken ovalbumin upstream promoter-transcription factor II enhances invasiveness of human lung carcinoma cells
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DOI：
10.1158/0008-5472.can-03-1185
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发表时间：
2004-08-01
期刊：
影响因子：
11.2
通讯作者：
Hu, J
中科院分区：
文献类型：
--
作者：
Navab, R;Gonzalez-Santos, JM;Hu, J
鸡卵清蛋白上游启动子转录因子11（COUP-TFII）在血管生成和发育中起重要作用。它在肿瘤细胞系中差异表达，但其在致癌作用中的作用在很大程度上是未知的。我们在这里证明，当COUP-TFII表达时，非侵袭性人肺癌细胞变得具有侵袭性。细胞外基质降解蛋白酶，如基质金属蛋白酶2和尿激酶型纤溶酶原激活剂的表达上调。通过用COUP-TFII蛋白转导不同的人肺癌细胞系以及通过使用反义表达证实了这一发现。除了细胞外金属蛋白酶活性增加外，我们还观察到COUP-TFII转染的人肺癌细胞中肌动蛋白丝的解体和粘着斑激酶的磷酸化。这些结果表明，COUP-TFII可能被认为是一个新的抗癌治疗的目标。
Chicken ovalbumin upstream promoter-transcription factor 11 (COUP-TFII) plays an essential role in angiogenesis and development. It is differentially expressed in tumor cell lines, but its role in carcinogenesis is largely unknown. We demonstrate here that noninvasive human lung cancer cells become invasive when COUP-TFII was expressed. The expression of extracellular matrix degrading proteinases, such as matrix metalloproteinase 2 and urokinase-type plasminogen activator, was up-regulated in these cells. This finding was confirmed by transduction of different human lung cancer cell lines with COUP-TFII protein and also by using antisense expression. We observed disorganization of actin filaments and focal adhesion kinase phosphorylation in COUP-TFII-transfected human lung cancer cells in addition to the increase in extracellular metalloproteinase activity. These results suggest that COUP-TFII may be considered as a new target for anticancer therapies.