Dosne Pasqualini C
División Medicina Experimental, ILEX-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
Medicina (B Aires). 1997;57 Suppl 2:3-18.
The discovery of RNA oncoviruses dates back to 1911 when Rous isolated the avian virus which is the cause of the sarcoma which bears his name and to 1936 when Bittner related the "milk factor" to the development of murine mammary cancer. During the 50s, the successive descriptions of virus-induced sarcoma-leukemias in mice led to the oncogene theory and gradually to the postulation of a viral origin of cancer. The discovery of the reverse transcriptase in 1970 led to the establishment of the Retroviridae family including both onco and lentiviruses. The decade of the 80s was marked by three fundamental discoveries which altered the concept of oncovirus: 1) oncogenes became established as part of the cellular genome converting retroviruses into occasional vectors of the oncogene; 2) as the T cell growth factor, interleukin-2, became available, the first human oncovirus, HTLV-I, was isolated and proved to be the cause of adult T cell leukemia; 3) HIV was isolated and classified as a lentivirus and as the cause of AIDS. A few years later the antioncogenes were discovered. Both oncogenes and anti-oncogenes were found to collaborate in the cell cycle, maintaining an equilibrium between proliferation and apoptosis. Today the viral theory has been replaced by the gene theory of cancer which postulates that neoplastic transformation is the result of a cascade of events which include uncorrected DNA errors, blocking of apoptosis, activation of oncogenes and deletion of antioncogenes. At the present time, the intriguing question for retrovirologists is the role played by endogenous retroviruses which in man occupy up to 0.1% of the cellular genome.
RNA肿瘤病毒的发现可追溯到1911年,当时劳斯分离出了一种禽病毒,该病毒是一种肉瘤的病因,这种肉瘤以他的名字命名;还可追溯到1936年,当时比特纳将“乳汁因子”与小鼠乳腺癌的发生联系起来。在20世纪50年代,对小鼠中病毒诱导的肉瘤白血病的相继描述导致了癌基因理论的产生,并逐渐形成了癌症病毒起源的假说。1970年逆转录酶的发现导致了逆转录病毒科的建立,该科包括致癌病毒和慢病毒。20世纪80年代这十年以三项重大发现为标志,这些发现改变了肿瘤病毒的概念:1)癌基因被确认为细胞基因组的一部分,使逆转录病毒成为癌基因的偶然载体;2)随着T细胞生长因子白细胞介素-2的问世,第一种人类肿瘤病毒HTLV-I被分离出来,并被证明是成人T细胞白血病的病因;3)HIV被分离出来并被归类为慢病毒,是艾滋病的病因。几年后,抗癌基因被发现。人们发现癌基因和抗癌基因在细胞周期中协同作用,维持增殖和凋亡之间的平衡。如今,病毒理论已被癌症基因理论所取代,该理论假定肿瘤转化是一系列事件的结果,这些事件包括未纠正的DNA错误、凋亡的阻断、癌基因的激活和抗癌基因的缺失。目前,逆转录病毒学家面临的一个有趣问题是内源性逆转录病毒所起的作用,内源性逆转录病毒在人类细胞基因组中所占比例高达0.1%。