Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors.
Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors.
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DOI：
10.1083/jcb.136.4.935
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发表时间：
1997-02-24
期刊：
影响因子：
--
通讯作者：
Schäfer R
中科院分区：
文献类型：
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作者：
Sers C;Emmenegger U;Husmann K;Bucher K;Andres AC;Schäfer R
H-rev 107基因是一种新的II类肿瘤抑制基因，其在HRAS转化细胞系中的可逆下调和生长抑制能力被定义。H-rev 107 cDNA在HRAS转化的ANR 4肝癌细胞或FE-8成纤维细胞中过表达导致集落形成减少75%。H-rev 107转染子的细胞群在裸鼠中显示出减弱的肿瘤形成。从肿瘤中分离或在细胞培养物中维持较长时间的细胞不再表现出可检测水平的H-rev 107蛋白，这表明在体外和体内对H-rev 107表达的强选择。缺少25个氨基酸的COOH末端膜相关结构域的截短形式的H-rev 107的表达对体外增殖具有较弱的抑制作用，并且不能减弱裸鼠中的肿瘤生长。H-rev 107 mRNA在大多数成年大鼠组织中表达，免疫组化分析显示该蛋白在胃、结肠和小肠、肾、膀胱、食管以及气管和支气管上皮的分化上皮细胞中表达。H-rev 107基因转录在来自肝、肾和胰腺肿瘤的大鼠细胞系以及表达RAS转基因的实验性乳腺肿瘤中下调。在结肠癌细胞系中，只能检测到微量的蛋白质。因此，H-rev 107表达的下调可能发生在mRNA或蛋白质水平。
The H-rev107 gene is a new class II tumor suppressor, as defined by its reversible downregulation and growth-inhibiting capacity in HRAS transformed cell lines. Overexpression of the H-rev107 cDNA in HRAS-transformed ANR4 hepatoma cells or in FE-8 fibroblasts resulted in 75% reduction of colony formation. Cell populations of H-rev107 transfectants showed an attenuated tumor formation in nude mice. Cells explanted from tumors or maintained in cell culture for an extended period of time no longer exhibited detectable levels of the H-rev107 protein, suggesting strong selection against H-rev107 expression in vitro and in vivo. Expression of the truncated form of H-rev107 lacking the COOH-terminal membrane associated domain of 25 amino acids, had a weaker inhibitory effect on proliferation in vitro and was unable to attenuate tumor growth in nude mice. The H-rev107 mRNA is expressed in most adult rat tissues, and immunohistochemical analysis showed expression of the protein in differentiated epithelial cells of stomach, of colon and small intestine, in kidney, bladder, esophagus, and in tracheal and bronchial epithelium. H-rev107 gene transcription is downregulated in rat cell lines derived from liver, kidney, and pancreatic tumors and also in experimental mammary tumors expressing a RAS transgene. In colon carcinoma cell lines only minute amounts of protein were detectable. Thus, downregulation of H-rev107 expression may occur at the level of mRNA or protein.