Enzootic nasal tumor virus type 2 envelope of goats acts as a retroviral oncogene in cell transformation
Enzootic nasal tumor virus type 2 envelope of goats acts as a retroviral oncogene in cell transformation
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DOI：
10.1007/s11262-020-01808-7
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发表时间：
2020-11-05
期刊：
影响因子：
1.6
通讯作者：
Maenaka，Katsumi
中科院分区：
文献类型：
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作者：
Maeda，Naoyoshi;Inoshima，Yasuo;Maenaka，Katsumi
1型地方性鼻肿瘤病毒（ENTV-1）（绵羊鼻肿瘤病毒）和2型地方性鼻肿瘤病毒（ENTV-2）分别是绵羊和山羊地方性鼻腺癌（ENA）的病原体。虽然ENTV-1和ENTV-2的核苷酸和氨基酸序列非常相似，但它们被认为是遗传学上不同的病毒。ENTV-1的包膜蛋白在上皮细胞和成纤维细胞的体外转化中作为癌蛋白发挥作用。因此，它是ENA体内肿瘤发生的主要决定因素。据我们所知，以前没有研究详细报道ENTV-2在ENA肿瘤发生中的作用。在此，为了研究ENTV-2致山羊ENA肿瘤的分子机制，我们试图鉴定ENTV-2包膜的转化潜力，并研究致癌转化中细胞信号通路的激活。我们的研究结果证实，ENTV-2包膜能够在体外诱导大鼠细胞系的致癌转化。此外，我们发现MAPK，Akt，和p38组成型激活ENTV-2病毒转化的克隆细胞。此外，抑制剂实验表明MEK-MAPK和PI 3 K-Akt信号通路参与了ENTV-2病毒诱导的细胞转化。这些数据表明ENTV-2包膜可以通过ENTV-1包膜也利用的信号传导途径诱导致癌转化。
Enzootic nasal tumor virus type 1 (ENTV-1) (ovine nasal tumor virus) and ENTV-2 (caprine nasal tumor virus) are known to be causative agents of enzootic nasal adenocarcinoma (ENA) in sheep and goats, respectively. Although the nucleotide and amino acid sequences of ENTV-1 and ENTV-2 are quite similar, they are recognized as phylogenetically distinct viruses. The envelope protein of ENTV-1 functions as an oncoprotein in the in vitro transformation of epithelial cells and fibroblasts. Thus, it is the primary determinant of in vivo tumorigenesis in ENA. As per our knowledge, no previous studies have reported in detail the role of ENTV-2 in ENA tumorigenesis. Here, in order to investigate the molecular mechanism of caprine ENA oncogenesis by ENTV-2, we have attempted to identify the transforming potential of ENTV-2 envelope, and investigated the activation of cell signaling pathways in oncogenic transformation. Our findings confirmed that ENTV-2 envelope was capable of inducing oncogenic transformation of rat cell lines in vitro. Further, we found that MAPK, Akt, and p38 were constitutively activated in ENTV-2 envelope-transformed clone cells. In addition, inhibitor experiments revealed that MEK-MAPK and PI3K-Akt signaling pathways are involved in the ENTV-2 envelope-induced cell transformation. These data indicate that ENTV-2 envelope could induce oncogenic transformation by signaling pathways that are also utilized by ENTV-1 envelope.