Heterogeneity in state and expression of viral DNA in polyoma virus-induced tumors of the mouse.
Heterogeneity in state and expression of viral DNA in polyoma virus-induced tumors of the mouse.
复制标题
多瘤病毒诱导的小鼠肿瘤中病毒 DNA 状态和表达的异质性。
DOI：
10.1016/0042-6822(92)90476-6
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发表时间：
1992
期刊：
影响因子：
3.7
通讯作者：
Benjamin,TL
中科院分区：
文献类型：
--
作者：
Talmage,DA;Freund,R;Dubensky,T;Salcedo,M;Gariglio,P;Rangel,LM;Dawe,CJ;Benjamin,TL
我们结合生物化学和原位方法，检测了多瘤病毒DNA在典型上皮和间叶肿瘤中的状态和表达。结果显示，在肿瘤类型之间以及在个体肿瘤内的不同区域中，就病毒DNA的拷贝数、缺失的存在或不存在以及早期和晚期病毒蛋白的表达而言，存在广泛的差异。上皮性肿瘤表现出最大的异质性。在所有这些肿瘤中发现了高拷贝游离病毒DNA，经常伴有缺失。一部分游离的病毒DNA可作为转录活性的微型染色体回收。三个不同的细胞亚群区分原位分析。1型细胞显示高拷贝游离病毒DNA，并表达主要病毒衣壳蛋白VP 1;这些细胞似乎处于生产性（裂解性）病毒感染的不同阶段。一些生产性感染的细胞能够进行有丝分裂，在这些细胞的一部分，VP 1被发现与有丝分裂纺锤体密切相关。2型细胞含有高拷贝游离DNA，但不表达VP 1;通过一些未知的机制，这些细胞表现出对晚期基因表达和裂解性感染的复制后阻断。3型细胞仅含有低拷贝，推测整合的病毒DNA，不表达VP 1;因此它们类似于病毒在体外转化的细胞。上皮肿瘤包含这些亚群的可变混合物，而间叶肿瘤仅由3型细胞组成。在病毒细胞相互作用的差异进行了讨论，在其可能的影响，在肿瘤发展
We have examined the state and expression of polyoma viral DNA in representative epithelial and mesenchymal tumors, using a combination of biochemical andin situmethods. Results showed wide variations among tumor types and also in different regions within individual tumors, with respect to copy number of viral DNA, presence or absence of deletions, and expression of early and late viral proteins. Epithelial tumors showed the greatest heterogeneity. High copy free viral DNA, frequently with deletions, was found in all such tumors. A portion of free viral DNA was recoverable as transcriptionally active minichromosomes. Three distinct subpopulations of cells were distinguished byin situanalyses. Type 1 cells showed high copy free viral DNA and expressed the major viral capsid protein VP1; these cells appeared to be at various stages of productive (lytic) viral infection. Some productively infected cells were able to undergo mitosis; in a portion of these cells, VP1 was found in close association with the mitotic spindle. Type 2 cells contained high copy free DNA but did not express VP1; by some unknown mechanism, these cells manifest a post-replication block to late gene expression and lytic infection. Type 3 cells contained only low copy, presumably integrated, viral DNA and expressed no VP1; they thus resemble cells transformedin vitroby the virus. Epithelial tumors contained variable mixtures of these subpopulations, while mesenchymal tumors were composed of Type 3 cells only. Differences in virus-cell interactions are discussed in terms of their possible implications in tumor development