Activation of the Mlvi-1/mis1/pvt-1 locus in Moloney murine leukemia virus-induced T-cell lymphomas.
Activation of the Mlvi-1/mis1/pvt-1 locus in Moloney murine leukemia virus-induced T-cell lymphomas.
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莫洛尼鼠白血病病毒诱导的 T 细胞淋巴瘤中 Mlvi-1/mis1/pvt-1 位点的激活。
DOI：
10.1073/pnas.86.14.5487
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发表时间：
1989
影响因子：
11.1
通讯作者：
Bear,SE
中科院分区：
文献类型：
--
作者：
Tsichlis,PN;Shepherd,BM;Bear,SE
Mlvi-1/mis-1/pvt-1基因座位于c-myc原癌基因3'端约270个酶对，最初被发现是Moloney鼠白血病病毒诱导的大鼠T细胞淋巴瘤中前病毒整合的共同区域。同一位点随后被证明与c-myc共扩增，并参与多种人类和动物肿瘤的染色体易位。在Moloney鼠白血病病毒诱导的大鼠T细胞淋巴瘤中，Mlvi-1中的前病毒整合激活c-myc原癌基因本文报道的研究旨在确定除了c-myc的激活外，前病毒整合是否影响其他邻近基因的表达。前病毒整合显示发生在由不间断DNA区域分隔的三个簇中。所有三个簇中的前病毒都以单转录方向整合，并且它们看起来是完整的。系统杂交的Mlvi-1克隆大鼠，小鼠和人类基因组DNA显示三个补丁的进化保守序列。其中两个被定位在前病毒靶向的区域，第三个被定位在前病毒簇的5'端。从整合的前病毒的5'保守序列衍生的探针检测在Mlvi-1或邻近的Mlvi-4和c-myc基因座中携带前病毒的肿瘤中的肿瘤特异性RNA转录物。然而，最高水平的RNA转录本表达出现在该区域不携带前病毒的CD 4 + CD 8+肿瘤细胞系中。我们的结论是，在这个区域插入前病毒激活c-myc和另一个基因，位于紧邻的集成Mlvi-1前病毒，并可能在T细胞发育调节。
The Mlvi-1/mis-1/pvt-1 locus, located approximately 270 kilobase pairs 3' of the c-myc protooncogene, was originally discovered as a common region of provirus integration in Moloney murine leukemia virus-induced rat T-cell lymphomas. The same locus was shown subsequently to be coamplified with c-myc and to be involved in chromosomal translocations in a variety of human and animal neoplasms. Provirus integration in Mlvi-1 in Moloney murine leukemia virus-induced rat T-cell lymphomas activates the c-myc protooncogene. The studies reported here were aimed to determine whether, in addition to the activation of c-myc, provirus integration affected the expression of other neighboring genes. Provirus integration was shown to occur in three clusters separated by regions of uninterrupted DNA. The proviruses in all three clusters had integrated in a single-transcriptional orientation, and they appeared intact. Systematic hybridization of Mlvi-1 clones to rat, mouse, and human genomic DNA revealed three patches of evolutionarily conserved sequences. Two of them were mapped in regions targeted by the provirus, and the third was mapped immediately 5' to the provirus clusters. A probe derived from the conserved sequences 5' of the integrated proviruses detected a tumor-specific RNA transcript in tumors carrying a provirus in Mlvi-1 or in the neighboring Mlvi-4 and c-myc loci. The highest level of RNA transcript expression, however, was seen in a CD4+ CD8+ tumor cell line that was not carrying a provirus in this region. We conclude that provirus insertion in this region activates both c-myc and another gene that is located in the immediate vicinity of the integrated Mlvi-1 proviruses and may be developmentally regulated in T cells.