N-myc can cooperate with ras to transform normal cells in culture.
N-myc can cooperate with ras to transform normal cells in culture.
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N-myc可以与ras协同转化培养中的正常细胞。
DOI：
10.1073/pnas.82.16.5455
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发表时间：
1985
影响因子：
11.1
通讯作者：
Alt,FW
中科院分区：
文献类型：
--
作者：
Yancopoulos,GD;Nisen,PD;Tesfaye,A;Kohl,NE;Goldfarb,MP;Alt,FW
N-myc是一种与c-myc原癌基因同源的细胞基因，在一组高度受限的相关肿瘤中经常被扩增和过表达，最明显的是神经母细胞瘤和视网膜母细胞瘤。我们通过确定N-myc在组织培养中转化原代细胞的能力，研究了N-myc可能在这些肿瘤的发生中发挥因果作用的可能性。利用一个N-myc表达构建体能够产生不受调控的全长小鼠N-myc mRNA水平，我们证明了不受调控的N-myc基因可以与活化的Ha-ras癌基因合作，以与不受调控的c-myc癌基因没有区别的方式导致正常胚胎成纤维细胞的致瘤性转化。从N-myc/ras转化灶中建立的细胞系表达高水平的N-myc基因，这些细胞系在软琼脂中生长和在同基因大鼠中引起肿瘤的能力与c-myc/ras转化细胞系相似。这些结果表明，N-myc确实编码c-myc样转化活性，并且这种转化活性对于N-myc通常扩增或过表达的非常有限的肿瘤组不是特异性的。
N-myc, a cellular gene bearing homology to the c-myc protooncogene, is frequently amplified and overexpressed in a highly restricted set of related tumors, most notably neuroblastomas and retinoblastomas. We have examined the possibility that N-myc may play a causal role in the genesis of these tumors by defining its ability to transform primary cells in tissue culture. Using an N-myc expression construct capable of producing constitutively deregulated levels of full-length murine N-myc mRNA, we demonstrate that a deregulated N-myc gene can cooperate with the activated Ha-ras oncogene to cause tumorigenic conversion of normal embryonic fibroblasts in a manner indistinguishable from the deregulated c-myc oncogene. Cell lines established from N-myc/ras-transformed foci express high levels of the N-myc gene, and such lines are similar to c-myc/ras transformants in their ability to grow in soft agar and cause tumors in syngeneic rats. These results illustrate that N-myc does encode a c-myc-like transforming activity and that this transforming activity is not specific for the very restricted set of tumors in which N-myc is normally amplified or overexpressed.