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[转基因小鼠中的肿瘤发生]

[Oncogenesis in transgenic mice].

作者信息

Shvemberger I N, Ermilov A N

出版信息

Tsitologiia. 1994;36(2):131-47.

PMID:7809963
Abstract

Oncogenesis in transgenic mice is at present a model, most adequately reflecting the natural conditions of tumor development. One of more important traits of this model is that it allows to study malignant growth simultaneously at all the structure-function levels in the context of the whole organism. This paper is a review of results of a series of experiments in which the localization of tumors was dependent or independent on the tissue specificity of a promoter, as well as development of multiple tumors with the use of viral regulatory sequences in genetic constructions. It has been shown that although a transgene is expressed in most of the tissues, tumors develop in some particular tissues only. These observations are interpreted by some authors in favour of the concept of multistep cancerogenesis. In this view, of primary importance are the results of studies on oncogenesis in transgenic mice, which contradict this concept and are regarded by their authors as an evidence of the possibility of a one-step transformation of normal cell into malignant one. The analysis of the obtained material enabled us to put forward an assumption that the key role in oncogenesis is played not only by certain genetic disturbances, but also by multi-level homeostatic mechanisms. Apparently, it is just the transgenic mice with cellular or viral oncogenes in their genome that represent a more adequate model for the detection of certain molecular-biological mechanisms underlying these disturbances. Also, of much importance is abundant material accumulated by now on oncogenesis of transgenic mice which shows a possibility of the effective use of various genetic constructions with prokaryotic and eukaryotic regulatory sequences, a possibility to induce not only tumors of some particular tissues, but also multiple hyperplastic and neoplastic changes in one and the same mouse. Development of tumors in such transgenic mice can be regarded as a model of different types of cancer disease.

摘要

目前,转基因小鼠中的肿瘤发生是一种最能充分反映肿瘤发展自然条件的模型。该模型的一个更重要的特征是,它允许在整个生物体的背景下,同时在所有结构 - 功能水平上研究恶性生长。本文综述了一系列实验的结果,这些实验中肿瘤的定位取决于或不取决于启动子的组织特异性,以及在基因构建中使用病毒调控序列诱导多发性肿瘤的情况。已经表明,尽管转基因在大多数组织中表达,但肿瘤仅在某些特定组织中发生。一些作者对这些观察结果的解释支持多步骤癌症发生的概念。按照这种观点,转基因小鼠肿瘤发生研究的结果至关重要,这些结果与该概念相矛盾,其作者将其视为正常细胞一步转化为恶性细胞可能性的证据。对所得材料的分析使我们能够提出一个假设,即在肿瘤发生中起关键作用的不仅是某些基因干扰,还有多层次的稳态机制。显然,基因组中带有细胞癌基因或病毒癌基因的转基因小鼠才是检测这些干扰背后某些分子生物学机制的更合适模型。同样重要的是,目前积累的大量关于转基因小鼠肿瘤发生的材料表明,有可能有效利用带有原核和真核调控序列的各种基因构建,不仅有可能诱导某些特定组织的肿瘤,还能在同一只小鼠中诱导多种增生性和肿瘤性变化。这种转基因小鼠中的肿瘤发展可被视为不同类型癌症疾病的模型。

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