C-myc activation in an unusual retrovirus-induced avian T-lymphoma resembling Marek's disease: proviral insertion 5' of exon one enhances the expression of an intron promoter.

C-myc activation in an unusual retrovirus-induced avian T-lymphoma resembling Marek's disease: proviral insertion 5' of exon one enhances the expression of an intron promoter.
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C-myc 在一种罕见的逆转录病毒诱导的类似于马立克氏​​病的禽 T 淋巴瘤中激活:前病毒插入外显子 1 的 5 增强了内含子启动子的表达。

DOI:
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发表时间:
1987
期刊:
Oncogene research
影响因子:
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通讯作者:
H. Kung
H. Kung
中科院分区:
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文献类型:
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作者:
R. Isfort;R. Witter;H. Kung

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非急性逆转录病毒诱导肿瘤的表征极大地促进了我们对宿主原癌基因激活机制的理解。在这里,我们报告了一种新发现的鸡淋巴瘤的分子特征,该淋巴瘤不涉及法氏囊。这种淋巴瘤由网状内皮增生病毒 (REV) 特异性诱导,其肿瘤位置和 T 细胞起源与马立克氏病(一种疱疹病毒诱导的 T 淋巴瘤)相似。我们证明 c-myc 是 REV 插入的特定目标位点。整合的原病毒全部位于 c-myc 编码外显子的上游,其中 60% 位于第一个非编码外显子的 5' 端。一半的原病毒的转录方向与 c-myc 基因相反。这种插入模式与同一病毒诱导的 B 淋巴瘤的模式相反。虽然这些 T 淋巴瘤中的一些原病毒使用 3' LTR 启动子来转录下游 c-myc 基因,但其他原病毒显然激活了位于第一个内含子中的常见、神秘的启动子。据我们所知,这是对非急性逆转录病毒诱导的禽类 T 淋巴瘤的首次分子描述。
Characterization of nonacute retrovirus-induced neoplasms have greatly facilitated our understanding of the mechanisms by which host protooncogenes are activated. Here we report the molecular characterization of a newly identified chicken lymphoma, which does not involve the bursa of Fabricius. This lymphoma, specifically induced by reticuloendotheliosis virus (REV), is similar in tumor location and T-cell origin to Marek's disease, a herpesvirus-induced T-lymphoma. We show the c-myc is the specific target locus for REV insertion. Integrated proviruses are all located upstream of the c-myc coding exons, and 60% are 5' to the first noncoding exon. One-half of the proviruses are oriented in the opposite transcriptional direction as the c-myc gene. This insertion pattern is in contrast to the pattern in B-lymphomas induced by the same virus. While some of the proviruses in these T-lymphomas used the 3' LTR promoter to transcribe the downstream c-myc gene, others apparently activated a common, cryptic promoter located in the first intron. To our knowledge, this is the first molecular description of an avian T-lymphoma induced by a nonacute retrovirus.