Nepveu A, Fahrlander P D, Yang J Q, Marcu K B
Nature. 1985;317(6036):440-3. doi: 10.1038/317440a0.
Chromosomal rearrangements involving the c-myc oncogene are a prevalent feature of plasmacytomas that arise after inoculating BALB/c mice with pristane and Abelson murine leukaemia virus (A-MuLV). With this observation in mind, we decided to determine if any genetic alterations of the c-myc locus could be observed in cells of a different type, when transformed in vitro by A-MuLV. Here we have analysed three independent A-MuLV-transformed NIH 3T3 lines (ANN-I, 54c12 and N25), and found that the c-myc locus is amplified 8-19-fold in each transformant. Quantitative S1 nuclease mapping performed on ANN-I and 54c12 RNAs demonstrated that: (1) c-myc messenger RNAs accumulated to double the levels found in NIH 3T3 cells; and (2) a shift in the use of the two normal c-myc transcription initiation sites (P1 and P2) occurred in favour of the 3' site, P2. Analysis of c-myc chromatin by DNase I treatment of 54c12 nuclei revealed that most, if not all, of the c-myc gene copies were transcriptionally competent. We present alternative ideas to explain why amplification of the c-myc gene occurs repeatedly in A-MuLV-transformed fibroblasts. Finally, we discuss our results in relation to the hypothesis linking the phenomenon of tumour progression with the amplification of oncogenes.
在用 pristane 和 Abelson 鼠白血病病毒（A-MuLV）接种 BALB/c 小鼠后产生的浆细胞瘤中，涉及 c-myc 癌基因的染色体重排是一个普遍特征。基于这一观察结果，我们决定确定当 A-MuLV 在体外转化不同类型的细胞时，是否能观察到 c-myc 基因座的任何遗传改变。在此，我们分析了三个独立的 A-MuLV 转化的 NIH 3T3 细胞系（ANN-I、54c12 和 N25），发现每个转化体中 c-myc 基因座扩增了 8 - 19 倍。对 ANN-I 和 54c12 RNA 进行的定量 S1 核酸酶图谱分析表明：（1）c-myc 信使 RNA 的积累量达到 NIH 3T3 细胞中发现水平的两倍；（2）在两个正常的 c-myc 转录起始位点（P1 和 P2）的使用上发生了转变，有利于 3' 位点 P2。通过用 DNase I 处理 54c12 细胞核来分析 c-myc 染色质，结果显示，即使不是全部，大多数 c-myc 基因拷贝在转录上都是有活性的。我们提出了一些其他观点来解释为什么 c-myc 基因在 A-MuLV 转化的成纤维细胞中会反复扩增。最后，我们结合将肿瘤进展现象与癌基因扩增联系起来的假说讨论了我们的结果。
