Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers
Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers
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DOI：
10.1016/s0304-3835(01)00763-7
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发表时间：
2002-06-06
期刊：
影响因子：
9.7
通讯作者：
Nagashima, K
中科院分区：
文献类型：
--
作者：
Nishihara, H;Tanaka, S;Nagashima, K
Crk 是一种信号转接蛋白，主要由 SH2 和 SH3 结构域组成。并已被证明在细胞增殖中发挥关键作用。分化、迁移。因为Crk最初是作为编码癌蛋白v-Crk的禽肉瘤病毒CT10被分离出来的。我们研究了 c-Crk 在人类癌症发生中的潜在作用。首先，为了分析c-Crk的基因突变，我们分离了含有Crk基因组和外显子/内含子结构的人类细菌人工染色体克隆，然而，聚合酶链反应-单链构象多态性方法未能显示Crk外显子中任何可能与癌变相关的基因组突变。其次，c-Crk-II 的免疫组织化学分析表明，c-Crk-II 的水平在大多数肿瘤中显着升高，特别是在结肠癌和肺癌中。此外，使用人肺癌细胞系的免疫印迹分析表明，c-Crk-II 的表达水平与 L 细胞的生长速率相关。 c-Crk-II表达水平升高可能与人类癌症的发生有关。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Crk is a signaling adaptor protein which is mostly composed of SH2 and SH3 domains. and has been shown to play a pivotal role in cell proliferation. differentiation, and migration. Because Crk was originally isolated as an avian sarcoma virus CT10 encoding oncoprotein v-Crk. we examined a potential role for c-Crk in the carcinogenesis of human cancers. First, to analyze gene mutations of c-Crk, we isolated a human bacterial artificial chromosome clone containing Crk genome and exon/intron structures, However, polymerase chain reaction-single strand conformation polymorphism methods failed to show any genomic mutations in the Crk exon which could be related to carcinogenesis. Second, immunohistochemical analysis of c-Crk-II demonstrated that the levels of c-Crk-II were significantly elevated in most of the tumors, particularly in the colon and lung cancers. Furthermore, immunoblot analysis using human lung cancer cell lines revealed that the expression levels of c-Crk-II were correlated to growth rates of L cells. The elevated expression levels of c-Crk-II might be related to the development of human cancers. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.