ACTIVATION OF THE MOUSE CELLULAR HARVEY-RAS GENE IN CHEMICALLY-INDUCED BENIGN SKIN PAPILLOMAS
ACTIVATION OF THE MOUSE CELLULAR HARVEY-RAS GENE IN CHEMICALLY-INDUCED BENIGN SKIN PAPILLOMAS
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DOI：
10.1038/307658a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
SMITH, J
中科院分区：
文献类型：
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作者：
BALMAIN, A;RAMSDEN, M;SMITH, J
许多人类和动物肿瘤发展的一个重要特征是出现恶性前良性病变，其中一些在向恶性发展的过程中会发生进一步的变化1 - 4。许多目前公认的多阶段癌变概念都是通过基于小鼠皮肤肿瘤化学诱导的实验模型发展起来的。在这个系统中，许多出现的恶性前乳头状瘤依赖于启动子，如果启动子治疗中断，它们似乎会消退，而另一些则发展成自主良性病变，在某些情况下，形成恶性癌5。虽然导致恶性肿瘤的事件的数量和性质尚不清楚，但DNA转染实验已经鉴定出一些可能在肿瘤细胞中发生定性改变的基因（参考文献6）。我们之前已经证明，来自化学致癌物诱导的可移植小鼠皮肤癌的DNA具有转化NIH/3T3细胞的能力，并且负责转化的基因是小鼠细胞哈维-拉斯基因（c-rasH）的激活形式7。我们现在已经研究了原癌基因获得转化活性的癌变阶段。我们证明在两种不同的小鼠品系中由化学致癌物诱导的原发性乳头状瘤具有激活的c-rasHgene。这构成了良性肿瘤的第一个报告，其中含有可检测的转化活性DNA。此外，与正常表皮相比，乳头状瘤中c-rasHgene转录物的稳态水平升高。
An important feature of the development of many human and animal tumours is the appearance of pre-malignant benign lesions, some of which undergo further changes during progression to malignancy1–4. Many of the currently accepted concepts of multi-stage carcinogenesis have been developed using an experimental model based on the chemical induction of tumours in mouse skin3,4. In this system, many of the pre-malignant papillomas which arise are promoter-dependent, and appear to regress if promoter treatment is interrupted, whereas others progress to form autonomous benign lesions and, in some cases, malignant carcinomas5. Although the number and nature of the events leading to malignancy are not known, DNA transfection experiments have led to the identification of several genes which may be qualitatively altered in tumour cells (see ref. 6 for review). We have previously shown that DNA from transplantable mouse skin carcinomas induced by chemical carcinogens has the ability to transform NIH/3T3 cells, and that the gene responsible for the transformation is an activated form of the mouse cellular Harvey-rasgene (c-rasH)7. We have now investigated the stage of carcinogenesis at which the proto-oncogene acquires transforming activity. We demonstrate that primary papillomas induced by chemical carcinogens in two different mouse strains have an activated c-rasHgene. This constitutes the first report of a benign tumour which contains DNA with detectable transforming activity. In addition, steady-state levels of c-rasHgene transcripts are elevated in the papillomas as compared with normal epidermis.