Morrison B W, Leder P
Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02115.
Oncogene. 1994 Dec;9(12):3417-26.
We have previously shown that each of four activated oncogenes (c-myc, neu, ras, and int-2) can serve as transgenic initiators of morphologically distinct adenocarcinomas of the murine mammary gland. Since abnormalities of these oncogenes are found frequently in human breast cancers, such differences are of particular interest. Thus, the distinctiveness of each murine tumor type might reflect a relationship between a specific oncogene and a susceptible target cell or might reflect distinctive changes brought about by the idiosyncratic action of each oncogene. We have identified six genes (two of them novel) expressed in tumors initiated by neu, but usually absent from tumors initiated by c-myc. The expression of these genes (kappa-casein, transferrin, cellular retinol binding protein I (CRBPI), WDNM1, and the two novel ones) cannot be induced in c-myc-initiated tumors by the introduction of an activated neu oncogene nor can their expression be inhibited in neu-initiated tumors by the introduction of c-myc. Therefore, these genes appear to represent markers of a cell type preferentially transformed by neu. Further analysis reveals that the six markers are also expressed by ras-initiated mammary tumors, but not by int-2-initiated tumors suggesting that neu/ras-initiated tumors share a common cellular lineage and/or a common signal transduction pathway. Interestingly, one of the novel marker genes (Mat-8) appears to encode a cell-surface chloride channel and the other, a secreted protein with homologies to glycosyl hydrolases, both of which might be useful for the diagnosis and treatment of specific mammary tumors.
我们之前已经表明，四种激活的癌基因（c-myc、neu、ras和int-2）中的每一种都可以作为转基因引发剂，引发形态上不同的小鼠乳腺腺癌。由于这些癌基因的异常在人类乳腺癌中经常被发现，所以这种差异特别令人感兴趣。因此，每种小鼠肿瘤类型的独特性可能反映了特定癌基因与易感靶细胞之间的关系，或者可能反映了每种癌基因的特异作用所带来的独特变化。我们已经鉴定出六个在由neu引发的肿瘤中表达，但在由c-myc引发的肿瘤中通常不存在的基因（其中两个是新基因）。这些基因（κ-酪蛋白、转铁蛋白、细胞视黄醇结合蛋白I（CRBPI）、WDNM1和两个新基因）的表达在c-myc引发的肿瘤中不能通过引入激活的neu癌基因来诱导，在neu引发的肿瘤中也不能通过引入c-myc来抑制。因此，这些基因似乎代表了一种优先被neu转化的细胞类型的标志物。进一步分析表明，这六个标志物在由ras引发的乳腺肿瘤中也有表达，但在由int-2引发的肿瘤中没有表达，这表明由neu/ras引发的肿瘤具有共同的细胞谱系和/或共同的信号转导途径。有趣的是，其中一个新的标志物基因（Mat-8）似乎编码一种细胞表面氯离子通道，另一个编码一种与糖基水解酶具有同源性的分泌蛋白，这两者都可能对特定乳腺肿瘤的诊断和治疗有用。
