Alexander W S, Bernard O, Cory S, Adams J M
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Oncogene. 1989 May;4(5):575-81.
Transgenic mice bearing c-myc driven by the immunoglobulin heavy chain enhancer (E mu) initially exhibit a preneoplastic lymphoproliferative syndrome from which clonal pre-B or B lymphomas develop at random. To investigate whether this transition involves the activation of oncogenes capable of transforming fibroblasts, we transfected DNA from 14 E mu-myc lymphomas into NIH3T3 cells and tested the tumorigenicity of the transfectants in nude mice. By this assay and subsequent direct analysis of the lymphoma mRNA by cDNA cloning or the polymerase chain reaction, two independent E mu-myc lymphomas were shown to contain an N-ras or a K-ras oncogene mutated at codon 61. When incorporated into a recombinant retrovirus, the mutant N-ras allele could collaborate with myc to transform preneoplastic E mu-myc bone marrow pre-B cells. These results indicate that spontaneous mutation of ras genes is one pathway to lymphomagenesis in E mu-myc mice but that many of the lymphomas arise in response to changes that do not register in fibroblasts.
携带由免疫球蛋白重链增强子（Eμ）驱动的c-myc的转基因小鼠最初表现出一种肿瘤前淋巴细胞增殖综合征，从中随机发生克隆性前B或B淋巴瘤。为了研究这种转变是否涉及能够转化成纤维细胞的癌基因的激活，我们将来自14个Eμ-myc淋巴瘤的DNA转染到NIH3T3细胞中，并在裸鼠中测试转染子的致瘤性。通过该试验以及随后通过cDNA克隆或聚合酶链反应对淋巴瘤mRNA进行直接分析，发现两个独立的Eμ-myc淋巴瘤含有在密码子61处发生突变的N-ras或K-ras癌基因。当突变的N-ras等位基因整合到重组逆转录病毒中时，它可以与myc协同作用，转化肿瘤前Eμ-myc骨髓前B细胞。这些结果表明，ras基因的自发突变是Eμ-myc小鼠淋巴瘤发生的一条途径，但许多淋巴瘤是对在成纤维细胞中未检测到的变化作出反应而产生的。
