Stenman G, Delorme E O, Lau C C, Sager R
Proc Natl Acad Sci U S A. 1987 Jan;84(1):184-8. doi: 10.1073/pnas.84.1.184.
In previous cytogenetic studies, trisomy for 3q was found to be the most frequent chromosome change associated with induced tumorigenicity by a variety of agents in Chinese hamster cells. Here we describe similar chromosome changes in 11 lines of CHEF/18 cells transfected with the mutant c-Ha-ras containing plasmid pSV2gptEJ. All 11 lines contained the transfected EJ gene and expressed increased levels of p21, the EJ gene product. Ten of the 11 lines were tumorigenic and all but 2 of these were trisomic for all or part of 3q. One line remained diploid and was nontumorigenic despite expressing elevated p21. Two tumorigenic lines from "hit-and-run" transfection with pSV2gpt were shown to express only control levels of p21, but they were trisomic for 3q. These results show that increased p21 expression is neither necessary nor sufficient for inducing tumorigenicity of CHEF cells. We propose that tumorigenicity in the transfected CHEF/18 cells of this study was induced by chromosome rearrangements, especially trisomy for 3q, that occurred at increased frequencies following transfection with pSV2gptEJ.
在以往的细胞遗传学研究中,发现3q三体是中国仓鼠细胞中与多种试剂诱导的肿瘤发生相关的最常见染色体变化。在此,我们描述了用含突变型c-Ha-ras的质粒pSV2gptEJ转染的11株CHEF/18细胞中的类似染色体变化。所有11株细胞均含有转染的EJ基因,并表达增加水平的p21(EJ基因产物)。11株细胞中有10株具有致瘤性,其中除2株外,其余所有细胞均为3q全部或部分三体。有1株细胞仍为二倍体,尽管表达升高的p21,但无致瘤性。用pSV2gpt进行“打了就跑”转染得到的2株致瘤细胞系显示仅表达对照水平的p21,但它们为3q三体。这些结果表明,p21表达增加对于诱导CHEF细胞的致瘤性既非必要条件也非充分条件。我们提出,本研究中转染的CHEF/18细胞的致瘤性是由染色体重排诱导的,尤其是3q三体,在用pSV2gptEJ转染后其发生频率增加。