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[逆转录病毒和癌基因与细胞基因组的相互作用。1]

[Interaction of retroviruses and oncogenes with the cellular genome. 1].

作者信息

Scherdin U, Hölzel F

机构信息

Abteilung Molekularbiologie, Physiologisch-Chemischen Instituts und Frauenklinik der Universität Hamburg.

出版信息

Arzneimittelforschung. 1987 Oct;37(10):1205-9.

PMID:2829931
Abstract

Due to the peculiar type of replication and genome structure, retroviruses (RNA tumor viruses) are characterized by an intensive interaction with the genome of the infected cell. For replication, transcription of the viral RNA genome into double-stranded DNA and subsequent integration of the viral information into the cellular genome are requisite. The recombinatory events with the cellular DNA provide ample opportunities to generate new viral genome structures with altered information and to influence the expression of cellular genes. The lack of specificity of the integration process may lead to inactivation of cellular genes by insertion mutagenesis. The enhancer and promoter sequences of the proviral LTR (long terminal repeat) regions are able to activate the expression of cellular genes in the neighborhood of integration sites. Transforming retroviruses have acquired cellular genes as oncogenes the transcriptional products of which may trans-activate other genes of the host cell. Retroviral infection may result in malignant transformation and alteration of the differentiation pattern of the invaded cell. Depending on the cell type, a loss of expression of cellular functions (dedifferentiation) or an induction of differentiation processes is noticeable. The demonstration of cellular oncogenes (proto-oncogenes) and their activation by retroviruses has initiated new perspectives in understanding the regulation of cell growth and differentiation as well as the formation of tumors at the molecular level.

摘要

由于逆转录病毒(RNA肿瘤病毒)独特的复制方式和基因组结构,其特点是与受感染细胞的基因组存在强烈相互作用。为了进行复制,病毒RNA基因组转录为双链DNA并随后将病毒信息整合到细胞基因组中是必不可少的。与细胞DNA的重组事件为产生具有改变信息的新病毒基因组结构以及影响细胞基因表达提供了充足机会。整合过程缺乏特异性可能导致通过插入诱变使细胞基因失活。前病毒长末端重复序列(LTR)区域的增强子和启动子序列能够激活整合位点附近细胞基因的表达。具有致癌性的逆转录病毒获得了细胞癌基因,其转录产物可能反式激活宿主细胞的其他基因。逆转录病毒感染可能导致侵袭细胞发生恶性转化并改变分化模式。根据细胞类型的不同,可以观察到细胞功能表达丧失(去分化)或分化过程的诱导。细胞癌基因(原癌基因)及其被逆转录病毒激活的发现,为在分子水平上理解细胞生长和分化的调控以及肿瘤形成开创了新的视角。

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