Transgenic mice and oncogenesis.

Transgenic mice and oncogenesis.
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转基因小鼠和肿瘤发生。

DOI:
--
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发表时间:
1988
影响因子:
29.7
通讯作者:
Jerry M. Adams
Jerry M. Adams
中科院分区:
医学1区
文献类型:
--
作者:
Suzanne Cory;Jerry M. Adams

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携带特定促癌基因的转基因小鼠的创造开启了肿瘤学令人兴奋的新时代。单个癌基因对不同细胞类型的生物学效应现在可以直接在活体动物中进行评估。虽然转基因动物在每个组织中携带引入的癌基因,但该基因的表达可能是广泛的或针对特定的细胞谱系,这取决于所选择的调节序列。转基因在已建立谱系的每一只动物中的行为应该是相同的,事实上,也许在给定类型的每一个细胞中也是相同的。因此,良好表征的转基因品系成为永久资源。也许这些转基因动物提供的最重要的机会是探索肿瘤前状态的可能性。人们可以尝试评估癌基因是否扰乱了特定谱系内的分化。扰动可能有助于描绘早期成熟阶段,并阐明如何控制分化。因此,关于原癌基因的正常生物学功能可能会出现新的见解。癌基因协同性的规则也可以在不同的细胞类型中进行评估。例如,可以从携带癌基因的肿瘤前动物中分离相关细胞,并尝试在体外用携带其他癌基因的逆转录病毒将其完全转化。另一方面,第二个癌基因可以简单地通过繁殖两个独立的转基因品系的小鼠来引入。虽然转基因癌基因的研究仍处于起步阶段,但已经获得了重要的新见解。本章简要概述了转基因动物是如何产生的,然后考虑我们目前的状况,
The creation of transgenic mice carrying specific cancer-promoting genes has opened an exciting new era in oncology. The biological effects of an individual oncogene on diverse cell types can now be assessed directly within the living animal. While transgenic animals bear the introduced oncogene in every tissue, expression of that gene may either be widespread or directed to a particular cell lineage, depending upon the regulatory sequences chosen. The transgene should behave identically in every animal of an established lineage and, indeed, perhaps in every cell of a given type. Thus, a well-characterized transgenic line becomes a permanent resource. Perhaps the most significant opportunity provided by these transgenic animals is the possibility of exploring the pre-neoplastic state. One can attempt to assess whether an oncogene has perturbed differentiation within particular lineages. The perturbations may help to delineate early matu­ ration stages and to clarify how differentiation is controlled. Thus, new insights may emerge regarding the normal biological functions of proto­ oncogenes. The rules for oncogene cooperativity can also be evaluated within diverse cell types. For example, one can isolate the relevant cells from a pre-neoplastic animal bearing an oncogene and attempt to trans­ form them fully in vitro with retroviruses carrying other oncogenes. Alter­ natively, the second oncogene could be introduced simply by breeding mice of two independent transgenic lines. While the study of transgenic oncogenes is still in its infancy, major new insights have already been gained. This chapter briefly summarizes how transgenic animals are produced, and then considers our current state of
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