Expression Data from Normal or ErbB2 Tumor Fibroblasts With or Without Ets2. Mus musculus

The mechanisms involved in epithelium-stroma interactions remain poorly understood, despite the importance of the microenvironment during tumorigenesis. Here, we studied the role of Ets2 transcrpiton factor in tumor associated fibroblasts in the MMTV-ErbB2 mammary tumor model. Inactivation of Ets2 specifically in fibroblasts using Fsp-cre significantly reduced tumor growth, in contrast to Ets2 inactivation in epithelium in which no differences in tumor growth were observed. Microarray analysis on isolated fibroblasts demonstrated the important role of Ets2 in remodeling of the extracellular matrix and angiogenesis in these cells. Tumors lacking Ets2 in fibroblats had diminished blood vessels. Our tumor specific gene signature was also represented in the stroma of human breast cancer patients. Collectively, our results suggest Ets2 uniquely contributes to angiogenesis from fribroblasts in the tumor microenvironment. Overall design: Primary mammary fibroblasts were isolated from mice with no oncogene with or without Ets2 and with the ErbB2 oncogene with or without Ets2, RNA was extracted and samples were submitted for Affymetrix gene expression arrays

上皮-间质（epithelium-stroma）相互作用的相关分子机制仍未被充分阐释，尽管肿瘤发生过程中肿瘤微环境的重要性已得到广泛认可。本研究以MMTV-ErbB2乳腺肿瘤模型为研究对象，探讨Ets2转录因子（Ets2 transcription factor）在肿瘤相关成纤维细胞中的功能。研究人员通过Fsp-cre系统特异性敲除成纤维细胞中的Ets2基因，可显著抑制肿瘤生长；与之形成鲜明对比的是，在上皮细胞中敲除Ets2后，肿瘤生长未出现任何显著差异。对分离得到的成纤维细胞进行微阵列（microarray）分析后发现，Ets2在这类细胞的细胞外基质重塑与血管生成过程中发挥关键调控作用。成纤维细胞缺失Ets2的肿瘤，其内部微血管密度显著降低。我们所构建的肿瘤特异性基因特征标签，在人类乳腺癌患者的肿瘤间质中同样得到了验证。综上，本研究结果表明，Ets2可通过肿瘤微环境中的成纤维细胞，特异性参与血管生成过程。实验整体设计：分别从仅带有或不带有Ets2且无致癌基因的小鼠，以及仅带有或不带有Ets2且携带ErbB2致癌基因的小鼠体内分离原代乳腺成纤维细胞，提取总RNA后送至Affymetrix基因表达芯片（Affymetrix gene expression arrays）平台进行检测。