Muschel R J, Nakahara K, Chu E, Pozzatti R, Liotta L A
Cancer Res. 1986 Aug;46(8):4104-8.
The hypothesis of tumor progression proposed by Nowell [P. C. Nowell, Science (Wash. DC), 194: 23-28, 1976] states that one mechanism for the development of the metastatic phenotype could be the induction of chromosomal instability. We have developed a new experimental system for studying the induction of the metastatic phenotype using early passage fibroblasts which become metastatic in nude mice after transformation with the Harvey ras oncogene [R. J. Muschel et al., Am. J. Pathol., 121: 1-8, 1985; R. Pozzatti et al., Science (Wash. DC), 232: 223-227, 1986]. Since the early passage fibroblasts themselves are diploid, we reasoned that this might be a system in which karyotypic change after tumor formation or metastasis might easily be evaluated. Thus, we performed cytogenetic analysis on multiple metastases and tumors which had been derived from cells transformed with the cellular Harvey ras1 oncogene and compared their karyotypes. The karyotypes of the cells isolated from 5 tumors and 14 metastases were, as far as we could determine, identical to those of the injected cells. This could easily be evaluated because of the two clones studied one was diploid; the other has a trisomy of chromosome 4 without any other detectable abnormality. These results suggest that in this system using nude mice, selection for a necessary or even advantageous chromosomal aberration does not occur during tumor formation or metastasis. Furthermore, they indicate that the presence of the ras gene itself does not induce chromosomal rearrangements or aneuploidy and that a cell can be both tumorigenic and metastatic yet remain diploid.
诺威尔[P. C. 诺威尔，《科学》（华盛顿特区），194: 23 - 28，1976]提出的肿瘤进展假说指出，转移表型发展的一种机制可能是染色体不稳定性的诱导。我们开发了一种新的实验系统，用于研究转移表型的诱导，该系统使用早期传代的成纤维细胞，这些细胞在用哈维ras癌基因转化后在裸鼠中发生转移[R. J. 马斯切尔等人，《美国病理学杂志》，121: 1 - 8，1985；R. 波扎蒂等人，《科学》（华盛顿特区），232: 223 - 227，1986]。由于早期传代的成纤维细胞本身是二倍体，我们推断这可能是一个在肿瘤形成或转移后容易评估核型变化的系统。因此，我们对源自用细胞哈维ras1癌基因转化的细胞的多个转移灶和肿瘤进行了细胞遗传学分析，并比较了它们的核型。就我们所能确定的而言，从5个肿瘤和14个转移灶中分离出的细胞的核型与注射细胞的核型相同。这很容易评估，因为在研究的两个克隆中，一个是二倍体；另一个有4号染色体三体，没有任何其他可检测到的异常。这些结果表明，在这个使用裸鼠的系统中，在肿瘤形成或转移过程中不会发生对必要甚至有利的染色体畸变的选择。此外，它们表明ras基因本身的存在不会诱导染色体重排或非整倍体，并且一个细胞可以既是致瘤性的又是转移性的，但仍然保持二倍体状态。
