Different transcriptional strategies for ccn2/ctgf gene induction between human chondrocytic and breast cancer cell lines
Different transcriptional strategies for ccn2/ctgf gene induction between human chondrocytic and breast cancer cell lines
复制标题
DOI：
10.1016/j.biochi.2006.12.006
复制
发表时间：
2007-03-01
期刊：
影响因子：
3.9
通讯作者：
Takigawa, Masaharu
中科院分区：
文献类型：
--
作者：
Eguchi, Takanori;Kubota, Satoshi;Takigawa, Masaharu
结缔组织生长因子（CTGF/CCN2）在软骨内骨形成中起关键作用；然而，CCN2也促进乳腺癌的血管生成和骨转移。软骨细胞HCS-2/8细胞和乳腺癌MDA231细胞产生的CCN2是任何其他细胞类型的6倍以上。在这项研究中，我们证明了这些细胞系采用不同的转录策略来诱导ccn2基因。软骨细胞中显性转录增强子的四个串联拷贝（4 x TRENDIC）与SV40促荧光素酶构建体嵌合连接，随后进行分析。在HCS-2/8细胞中，启动子活性提高了4倍（7倍），而在其他4个细胞系中（3-4倍）。在HCS-2/8细胞中检测到的trendic结合蛋白复合物的信号高于其他细胞系。此外，HCS-2/8核因子不仅强烈靶向TRENDIC，还强烈靶向ccn2启动子中先前报道的基础控制元件和新型增强元件。相比之下，在MDA231细胞中，高水平的ccn2基因诱导在很大程度上依赖于通过ccn2启动子中Smad结合元件的Smad信号传导。基于这些结果，我们提出了一个ccn2基因在软骨细胞系和乳腺癌细胞系之间的差异转录模型，因此暗示这些细胞利用不同的转录策略来获得在其他类型细胞中未观察到的增强的ccn2产生。(c) 2007年Elsevier Masson SAS。版权所有。
Connective tissue growth factor (CTGF/CCN2) plays a critical role in endochondral bone formation; however, CCN2 also promotes angiogenesis and bone metastasis in breast cancer. Chondrocytic HCS-2/8 cells and breast cancer MDA231 cells produce over 6 times more CCN2 than any other cell type. In this study, we demonstrate that these cell lines employ different transcriptional strategies for ccn2 gene induction. Four tandem copies of the dominant transcriptional enhancer in chondrocytes (4 x TRENDIC) were chimerically connected to an SV40 pro-moter-luciferase construct and subsequently analyzed. The enhancement of the promoter activity by 4 x TRENDIC was greater in the HCS-2/8 cells (7-fold) than in the other 4 cell lines (3-4 fold). The TRENDIC-binding protein complex was detected at a higher signal in the HCS-2/8 cells than in the other cell lines. In addition, the HCS-2/8 nuclear factors strongly targeted not only TRENDIC, but also the previously reported basal control element and a novel enhancer element in the ccn2 promoter. In contrast, high-level ccn2 gene induction in MDA231 cells was largely dependent on Smad signaling through the Smad-binding element in the ccn2 promoter. Based on these results, we propose a model of differential transcription of the ccn2 gene between the chondrocytic cell line and the breast cancer cell line, and therefore imply that these cells utilize distinct transcriptional strategies to obtain the enhanced CCN2 production that is not observed in other types of cells. (c) 2007 Elsevier Masson SAS. All rights reserved.