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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Telomerase reverse transcriptase expression elevated by avian leukosis virus integration in B cell lymphomas
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Telomerase reverse transcriptase expression elevated by avian leukosis virus integration in B cell lymphomas

机译：禽白血病病毒整合增加B细胞淋巴瘤端粒酶逆转录酶表达

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摘要

Simple retroviruses induce tumors by integrating into the host genome, activating cellular oncogenes and microRNAs, or inactivating tumor suppressor genes. The identification of these genes elucidates molecular mechanisms of tumorigenesis. In this study, we identified avian leukosis virus (ALV) proviral integration sites in rapid-onset B cell lymphomas arising ＜ 12 weeks after infection of chicken embryos. By using inverse PCR, 28 unique viral integration sites were identified in rapid-onset tumors. Integrations in the telomerase reverse transcriptase (TERT) promoter/enhancer region were observed in four different tumors, suggesting that this is a common integration site. These provirus integrations ranged from 217 to 2,584 bp upstream of the TERT transcription initiation site and were all in the opposite transcriptional orientation to TERT. Southern blots of tumor samples demonstrated that these integrations are clonal and therefore occurred early in the process of tumorigenesis. Real-time RT-PCR showed overexpression of TERT mRNA in tumors harboring viral integrations in the TERT promoter. Telomerase activity was also up-regulated in these tumors; however, telomere-length alterations were not detected. Furthermore, viral LTR sequences directly enhanced the expression of luciferase reporters containing the TERT promoter sequences. This study documents retroviral up-regulation of cellular TERT by insertional activation to initiate or enhance tumor progression.
机译：简单的逆转录病毒通过整合入宿主基因组，激活细胞癌基因和microRNA或灭活肿瘤抑制基因来诱导肿瘤。这些基因的鉴定阐明了肿瘤发生的分子机制。在这项研究中，我们在感染鸡胚后不到12周的快速发作B细胞淋巴瘤中鉴定了禽白血病病毒（ALV）前病毒整合位点。通过使用反向PCR，在快速发作的肿瘤中鉴定出28个独特的病毒整合位点。在四个不同的肿瘤中观察到端粒酶逆转录酶（TERT）启动子/增强子区域的整合，这表明这是一个常见的整合位点。这些前病毒整合在TERT转录起始位点上游的217到2,584 bp范围内，并且都与TERT处于相反的转录方向。肿瘤样品的Southern印迹证明这些整合是克隆性的，因此发生在肿瘤发生的早期。实时RT-PCR显示在TERT启动子中携带病毒整合的肿瘤中TERT mRNA的过表达。在这些肿瘤中，端粒酶活性也被上调。但是，没有检测到端粒长度改变。此外，病毒LTR序列直接增强了含有TERT启动子序列的荧光素酶报道分子的表达。这项研究记录了通过插入激活引发或增强肿瘤进展的细胞TERT逆转录病毒上调。

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