The analysis of malignancy by cell fusion. IX. Re-examination and clarification of the cytogenetic problem.
The analysis of malignancy by cell fusion. IX. Re-examination and clarification of the cytogenetic problem.
复制标题
通过细胞融合分析恶性肿瘤。
作者：
E. P. Evans;M. Burtenshaw;B. Brown;R. Hennion;H. Harris
以前的实验与恶性和二倍体小鼠细胞之间的杂交表明，在杂交瘤中，它最初被抑制的恶性肿瘤的重现在某些情况下与消除来自二倍体亲本细胞的染色体4有关。然而，在其他国家，情况似乎并非如此。在本研究中，我们重新研究了二倍体4号染色体在抑制恶性肿瘤中的作用，使用自然多态性的着丝粒异染色质，以确定杂交细胞中4号染色体的亲本来源。我们现在发现，二倍体4号染色体确实参与了我们检查过的所有肿瘤的恶性肿瘤抑制，包括癌、黑色素瘤、肉瘤和淋巴瘤。在这些恶性肿瘤细胞和二倍体成纤维细胞之间的所有杂交中，存在针对源自二倍体细胞的染色体4和有利于源自恶性细胞的染色体4的体内选择压力。这表明所有这些肿瘤中的4号染色体在某种程度上与二倍体成纤维细胞的4号染色体在功能上不同。在最初被抑制的杂交种中恶性肿瘤的再现可能是由于二倍体4号染色体数量的减少、恶性4号染色体数量的增加或两者兼而有之。二倍体4号染色体上负责抑制恶性肿瘤的基因以剂量依赖性方式起作用。
Previous experiments with crosses between malignant and diploid mouse cells had shown that the reappearance of malignancy in hybrids in which it was initially suppressed was associated in some cases with the elimination of the chromosomes 4 derived from the diploid parent cell. In others, however, this did not appear to be so. In the present study, we have re-examined the role of the diploid chromosomes 4 in the suppression of malignancy using natural polymorphisms of the centromeric heterochromatin to identify the parental origin of the chromosomes 4 in the hybrid cells. We now find that the diploid chromosomes 4 are indeed involved in the suppression of malignancy in all the tumours that we have examined, which include a carcinoma, a melanoma, a sarcoma and a lymphoma. In all crosses between these malignant tumour cells and diploid fibroblasts, there is selective pressure in vivo against the chromosomes 4 derived from the diploid cell and in favour of the chromosomes 4 derived from the malignant cell. This indicates that the chromosomes 4 in all these tumours are in some way functionally different from the chromosomes 4 of the diploid fibroblast. Reappearance of malignancy in hybrids in which it was initially suppressed may result from a reduction in the number of diploid chromosomes 4, an increase in the number of malignant chromosomes 4, or both. The gene on the diploid chromosome 4 responsible for the suppression of malignancy acts in a dose-dependent manner.