Colledge W H, Gebhardt A, Edge M D, Bell J C
Laboratory of Eukaryotic Molecular Genetics, National Institute for Medical Research, Mill Hill, London.
Oncogene. 1989 Jun;4(6):753-7.
Aberrations in nuclear proto-oncogene organisation and/or gene expression have been implicated in cell transformation mediated by the v-abl gene. For example, it has been suggested that amplification of the c-myc proto-oncogene is a co-operative event in v-abl induced fibroblast transformation. We have investigated amplification of the c-myc, p53 and c-fos nuclear proto-oncogenes in several Abelson murine leukaemia virus (A-MuLV) transformed fibroblast lines. None of these proto-oncogenes were detectably rearranged or amplified in v-abl transformed Swiss 3T3 lines. In contrast, NIH3T3 fibroblasts transformed by the v-abl gene consistently showed a 4 to 16-fold amplification of the c-myc gene. These data show that c-myc gene amplification is not an obligatory event associated with A-MuLV transformation, but may be restricted to cell lines derived from NIH3T3. c-myc gene amplification also did not correlate with a reduced latency period for tumour induction in nude mice. In addition, c-myc amplification was not selected during tumourigenesis, indicating that this event is not required for A-MuLV transformed Swiss 3T3 cells to display a full tumourigenic phenotype.
核原癌基因组织和/或基因表达的异常与v-abl基因介导的细胞转化有关。例如,有人提出c-myc原癌基因的扩增是v-abl诱导成纤维细胞转化中的一个协同事件。我们研究了几种阿贝尔森鼠白血病病毒(A-MuLV)转化的成纤维细胞系中c-myc、p53和c-fos核原癌基因的扩增情况。在v-abl转化的瑞士3T3细胞系中,这些原癌基因均未检测到可察觉的重排或扩增。相比之下,由v-abl基因转化的NIH3T3成纤维细胞始终显示出c-myc基因4至16倍的扩增。这些数据表明,c-myc基因扩增并非与A-MuLV转化相关的必然事件,而是可能局限于源自NIH3T3的细胞系。c-myc基因扩增也与裸鼠肿瘤诱导潜伏期的缩短无关。此外,在肿瘤发生过程中并未选择c-myc扩增,这表明该事件并非A-MuLV转化的瑞士3T3细胞展现完全致瘤表型所必需的。