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12型腺病毒在新生叙利亚仓鼠体内的致瘤作用。

Tumorigenesis by adenovirus type 12 in newborn Syrian hamsters.

作者信息

Hohlweg U, Dorn A, Hösel M, Webb D, Buettner R, Doerfler W

机构信息

Institute of Genetics, University of Cologne, 50931 Köln, Germany.

出版信息

Curr Top Microbiol Immunol. 2004;273:215-44. doi: 10.1007/978-3-662-05599-1_7.

Abstract

Ad12 oncogenesis in hamsters has been studied in detail to provide the following new data in this tumor model. Cells in the Ad12-induced tumors, often thought to be of neuronal origin, actually exhibit mesenchymal and neuronal characteristics and are probably of an undifferentiated derivation. Their intraperitoneal spread upon intramuscular injection of Ad12 adds another important new aspect. Differences in the integration patterns among the tumors suggest clonal origins from individual transformation events. Ad12 gene expression in the tumors is determined, at least in part, by the patterns of DNA methylation imprinted de novo upon the integrated Ad12 genomes. Differential Ad12 gene expression patterns, which have previously not been described in tumors, are an important parameter in Ad12 oncogenesis. The availability of cellular DNA arrays has opened up unprecedented possibilities to document changes in cellular transcription patterns, particularly of cancer-specific genes. These patterns exhibit differences and similarities among the different Ad12-induced tumors. Among the cellular genes, which are expressed in the Ad12-induced tumors, many are cancer-specific. We pursue the hypothesis that these alterations in cellular transcription patterns as a consequence of viral DNA integration and expression play an essential role in Ad12 oncogenesis.

摘要

为了在该肿瘤模型中提供以下新数据,对仓鼠中的腺病毒12型(Ad12)致癌作用进行了详细研究。Ad12诱导的肿瘤中的细胞通常被认为起源于神经元,但实际上表现出间充质和神经元特征,可能来源于未分化细胞。肌肉注射Ad12后它们在腹腔内的扩散增加了另一个重要的新情况。肿瘤之间整合模式的差异表明它们起源于个体转化事件的克隆。肿瘤中Ad12基因的表达至少部分由整合到Ad12基因组上的从头甲基化印记的DNA甲基化模式决定。以前在肿瘤中未描述过的Ad12基因差异表达模式是Ad12致癌作用的一个重要参数。细胞DNA阵列的可用性为记录细胞转录模式的变化,特别是癌症特异性基因的变化,开辟了前所未有的可能性。这些模式在不同的Ad12诱导的肿瘤之间表现出差异和相似性。在Ad12诱导的肿瘤中表达的细胞基因中,许多是癌症特异性的。我们探讨了这样一个假说,即病毒DNA整合和表达导致的细胞转录模式的这些改变在Ad12致癌作用中起重要作用。

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