Suppression of tissue factor expression, cofactor activity, and metastatic potential of murine melanoma cells by the N-terminal domain of adenovirus E1A 12S protein.
Suppression of tissue factor expression, cofactor activity, and metastatic potential of murine melanoma cells by the N-terminal domain of adenovirus E1A 12S protein.
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腺病毒 E1A 12S 蛋白 N 末端结构域抑制小鼠黑色素瘤细胞的组织因子表达、辅因子活性和转移潜力。
DOI：
10.1002/jcb.10099
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发表时间：
2002
影响因子：
4
通讯作者：
KelmJr,RobertJ
中科院分区：
文献类型：
--
作者：
Voigtländer,Constanze;Rand,Arlymae;Liu,Su-Ling;Wilson,TimothyJ;Pittelkow,MarkR;Getz,MichaelJ;KelmJr,RobertJ
组织因子是血液凝固的细胞起始因子，已被认为是人黑色素瘤细胞转移潜能的决定因素。在这里，我们报告了已知转移行为的小鼠黑色素瘤细胞系中组织因子的差异表达是由AP-1依赖性和12 S E1 A癌蛋白抑制性基因转录介导的。当与弱转移性C10细胞相比时，高转移性M4细胞具有升高水平的组织因子辅因子活性、转染的启动子活性和含有Fra-1的异源二聚体AP-1 DNA结合复合物。腺病毒E1 A 12 S癌蛋白的瞬时共表达强烈抑制了AP-1驱动的组织因子报告基因的转录，表明N末端E1 A相互作用辅激活因子的额外需求。CBP/p300结合缺陷的E1 A突变体的稳定表达未能抑制M4细胞的组织因子表达和实验转移，而表达野生型E1 A的克隆在体内表现出组织因子辅因子活性和转移潜力大大降低。在含有野生型E1 A的细胞中过表达功能性组织因子未能恢复高转移性M4表型，这表明需要额外的E1 A响应性和CBP/p300依赖性基因来促进小鼠黑色素瘤细胞的转移，这些细胞表现出高组织因子表达和辅因子活性。J.细胞。85：54-71，2002.© 2002 Wiley利斯公司
Tissue factor, the cellular initiator of blood coagulation, has been implicated as a determinant of metastatic potential in human melanoma cells. Here, we report that differential expression of tissue factor in murine melanoma cell lines of known metastatic behavior is mediated by AP‐1‐dependent and 12S E1A oncoprotein‐repressible gene transcription. When compared to weakly metastatic C10 cells, highly metastatic M4 cells possessed elevated levels of tissue factor cofactor activity, transfected promoter activity, and heterodimeric AP‐1 DNA‐binding complexes containing Fra‐1. Transient co‐expression of the adenovirus E1A 12S oncoprotein strongly repressed transcription of an AP‐1‐driven tissue factor reporter gene indicating the additional requirement ofN‐terminal E1A‐interacting coactivators. Stable expression of E1A mutants defective in CBP/p300‐binding failed to suppress tissue factor expression and experimental metastasis by M4 cells while clones expressing wild type E1A exhibited greatly reduced tissue factor cofactor activity and metastatic potential in vivo. Overexpression of functional tissue factor in cells containing wild type E1A failed to restore the highly metastatic M4 phenotype suggesting that additional E1A‐responsive and CBP/p300‐dependent genes are required to facilitate metastasis of murine melanoma cells demonstrating high tissue factor expression and cofactor activity. J. Cell. Biochem. 85: 54–71, 2002. © 2002 Wiley‐Liss, Inc.