ROLE OF DOUBLE MINUTES AND HSR MARKERS IN TUMOR CELLS

我们正在调查结构组织和功能 染色体异常在肿瘤细胞中的意义(1) 均一染色区域(HSRs)和(2)双微小染色体 (DMS)。我们已获得证据表明DM和HSR在相关的 Y1小鼠肾上腺皮质肿瘤细胞系在分子水平上相似 基因扩增过程中的组成和结果。一项分析 在3T3小鼠细胞的转化衍生细胞中的DM显示，DM在 这些细胞也是基因扩增的结果，但扩增的 序列与Y1细胞中的序列不同。我们已经证明了 与肿瘤转化基因(癌基因)相关的细胞序列 柯尔斯滕肉瘤病毒(Ki-ras)在Y1中扩增30-60倍 细胞中，扩增出的序列存在于DM和HSR上。此外， 细胞Ki-ras特异性mRNA和编码蛋白p21的水平 因为这种基因在这些细胞中是升高的。正在进行的研究应该 提供有关以下方面的信息：(1)\扩增DNA的组织； (2)扩增的基因数量；及(3)基因扩增的机制。 细胞癌基因的扩增和增强表达可能 有助于启动和/或维持肿瘤 一些细胞的转化。(一)

We are investigating the structural organization and functional significance in tumor cells of chromosomal anomalies termed (1) homogeneously staining regions (HSRs) and (2) double-minute chromosomes (DMs). We have obtained evidence that DMs and HSRs present in related lines of Y1 mouse adrenocortical tumor cells are similar in molecular composition and result from a process of gene amplification. An analysis of DMs in a transformed derivative of 3T3 mouse cells revealed that DMs in these cells also result from gene amplification, but the amplified sequences are different from those in the Y1 cells. We have demonstrated that cellular sequences related to the transforming gene (oncogene) of the Kirsten sarcoma virus (Ki-ras) are amplified 30-\to 60-fold in the Y1 cells, and the amplified sequences are present on DMs and HSRs. Further, the level of the cellular Ki-ras-specific mRNA and of the protein p21 coded for by this gene are elevated in these cells. Studies in progress should provide information concerning: (1)\the organization of the amplified DNA; (2)\the number of genes amplified; and (3)\the mechanisms by which the amplification and enhanced expression of cellular oncogenes might contribute to the initiation and/or maintenance of neoplastic transformation of some cells. (I)