Münger Karl
Department of Pathology and Harvard Center for Cancer Biology, Harvard Medical School, Boston, MA 02115-5701, USA.
Cancer Invest. 2002;20(1):71-81. doi: 10.1081/cnv-120000369.
Oncogenes were initially discovered as retrovirally transmitted tumor causing agents. The realization that such retroviral oncogenes constitute specifically altered versions of cellular genes-proto-oncogenes, was a landmark discovery that set the stage for the molecular and mechanistic era of cancer research. Moreover, the studies on oncogene functions have been instrumental in delineating many of the paradigms of cellular signal transduction. In contrast to the original studies in animals, oncogenic activation through retroviral transmission does not appear to be a major factor in human tumorigenesis. However, oncogenes are frequently activated by gain of function mutations or fusions with other genes, or they are aberrantly expressed due to amplification, increased promoter activity, or protein stabilization, and hence they play integral roles in the genesis of human tumors.
癌基因最初是作为逆转录病毒传播的致瘤因子被发现的。认识到这类逆转录病毒癌基因是细胞基因——原癌基因的特异性改变版本，是一项具有里程碑意义的发现，为癌症研究的分子和机制时代奠定了基础。此外，对癌基因功能的研究有助于阐明细胞信号转导的许多范例。与最初在动物身上进行的研究不同，通过逆转录病毒传播的致癌激活似乎不是人类肿瘤发生的主要因素。然而，癌基因经常通过功能获得性突变或与其他基因融合而被激活，或者由于扩增、启动子活性增加或蛋白质稳定而异常表达，因此它们在人类肿瘤的发生中起着不可或缺的作用。
