Hahne Jens Claus, Okuducu Ali Fuat, Kaminski Annette, Florin Alexandra, Soncin Fabrice, Wernert Nicolas
Institute of Pathology, University of Bonn, PO Box 2120, 53011 Bonn, Germany.
Oncogene. 2005 Aug 11;24(34):5384-8. doi: 10.1038/sj.onc.1208761.
Ets-1 is the prototype of the family of ETS transcription factors. In human tumors, Ets-1 is expressed in endothelial cells and fibroblasts of the tumor stroma and is proposed to play a role in tumor vascularization and invasion by upregulating expression of matrix-degrading proteases. In human carcinomas, Ets-1 is also expressed by neoplastic cells, but little is known about the functional implications of this observation. We have addressed the role of Ets-1 in epithelial HeLa tumor cells by selecting stably Ets-1 over and underexpressing HeLa cells. Ets-1 expression increases the transformed phenotype of HeLa cells, by promoting cell migration, invasion and anchorage-independent growth, while Ets-1 downregulation reduces cell attachment. In correlation with these results, Ets-1 upregulation increases integrinbeta2 expression but not that of other integrins. These results suggest that, in addition to its role in the tumor stroma, Ets-1 may also promote tumor development and progression by increasing neoplastic transformation.
Ets-1是ETS转录因子家族的原型。在人类肿瘤中,Ets-1在肿瘤基质的内皮细胞和成纤维细胞中表达,有人提出它通过上调基质降解蛋白酶的表达在肿瘤血管生成和侵袭中发挥作用。在人类癌症中,Ets-1也在肿瘤细胞中表达,但关于这一观察结果的功能意义知之甚少。我们通过选择稳定过表达和低表达Ets-1的HeLa细胞,研究了Ets-1在上皮性HeLa肿瘤细胞中的作用。Ets-1的表达通过促进细胞迁移、侵袭和非锚定依赖性生长增加了HeLa细胞的转化表型,而Ets-1的下调则降低了细胞附着。与这些结果相关的是,Ets-1的上调增加了整合素β2的表达,但其他整合素的表达没有增加。这些结果表明,除了在肿瘤基质中的作用外,Ets-1还可能通过增加肿瘤转化促进肿瘤的发展和进展。