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首页> 外文期刊>Molecular and Cellular Biology >A retrovirus carrying the K-fgf oncogene induces diffuse meningeal tumors and soft-tissue fibrosarcomas.
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A retrovirus carrying the K-fgf oncogene induces diffuse meningeal tumors and soft-tissue fibrosarcomas.

机译：携带K-fgf癌基因的逆转录病毒诱导弥漫性脑膜肿瘤和软组织纤维肉瘤。

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The K-fgf/hst oncogene encodes a growth factor of the fibroblast growth factor (FGF) family and transforms cells through an autocrine mechanism which requires extracellular activation of its receptor(s). To identify the cell and tissue targets of K-fgf oncogenic potential in vivo, we constructed a recombinant retrovirus carrying the human K-fgf cDNA and injected it, together with helper Moloney murine leukemia virus, into immunocompetent as well as nude mice. The original construct was highly transforming in tissue culture but produced no detectable pathologies in vivo with the exception of a single fibrosarcoma which arose after a long latency. The virus produced by this tumor appears to have undergone a complex series of recombination events involving the helper Moloney murine leukemia virus. It encodes an Env/K-FGF fusion protein whose expression is under the control of a hybrid long terminal repeat. This virus (designated MFS, for meningeal fibrosarcoma) induces tumors in mice with high frequency and short latency. These neoplasms consist of aggressive fibrosarcomas of soft tissue as well as diffuse meningeal tumors originating from the dura mater that surround the whole central nervous system and cause severe hydrocephalus. The Env/K-FGF fusion protein expressed by the MFS virus has retained all of the biological properties of native K-FGF, including secretion, mitogenic activity, heparin binding, and neutralization by anti-K-FGF antibodies. These and other results indicate that the tumors induced by the MFS virus result from the oncogenic potential of K-FGF.
机译：K-fgf / hst癌基因编码成纤维细胞生长因子（FGF）家族的生长因子，并通过自分泌机制转化细胞，该机制需要对其受体进行细胞外激活。为了确定体内K-fgf致癌潜能的细胞和组织靶标，我们构建了携带人K-fgf cDNA的重组逆转录病毒，并将其与辅助莫洛尼鼠白血病病毒一起注射入具有免疫能力的裸鼠。最初的构建体在组织培养中高度转化，但是在体内没有产生可检测到的病理，除了单个纤维肉瘤在长时间潜伏期后出现。该肿瘤产生的病毒似乎经历了一系列复杂的重组事件，涉及辅助性莫洛尼鼠白血病病毒。它编码一个Env / K-FGF融合蛋白，其表达受杂合长末端重复序列的控制。该病毒（命名为MFS，用于脑膜纤维肉瘤）以高频率和短潜伏期诱发小鼠肿瘤。这些肿瘤包括软组织的侵袭性纤维肉瘤以及源自硬脑膜的弥漫性脑膜肿瘤，其围绕整个中枢神经系统并引起严重的脑积水。由MFS病毒表达的Env / K-FGF融合蛋白保留了天然K-FGF的所有生物学特性，包括分泌，促有丝分裂活性，肝素结合以及抗K-FGF抗体的中和作用。这些和其他结果表明，由MFS病毒诱导的肿瘤是由K-FGF的致癌潜力引起的。

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