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由v-Myb介导的转化

Transformation by v-Myb.

作者信息

Lipsick J S, Wang D M

机构信息

Department of Pathology, Stanford University School of Medicine, California 94305-5324, USA.

出版信息

Oncogene. 1999 May 13;18(19):3047-55. doi: 10.1038/sj.onc.1202745.

Abstract

The v-myb oncogene of the avian myeloblastosis virus (AMV) is unique among known oncogenes in that it causes only acute leukemia in animals and transforms only hematopoietic cells in culture. AMV was discovered in the 1930s as a virus that caused a disease in chickens that is similar to acute myelogenous leukemia in humans (Hall et al., 1941). This avian retrovirus played an important role in the history of cancer research for two reasons. First, AMV was used to demonstrate that all oncogenic viruses did not contain a single cancer-causing principle. In particular, although both Rous sarcoma virus (RSV) and AMV could replicate in cultures of either embryonic fibroblasts or hematopoietic cells, RSV could transform only fibroblasts whereas AMV could transform only hematopoietic cells (Baluda, 1963; Durban and Boettiger, 1981a). Second, chickens infected with AMV develop remarkably high white counts and therefore their peripheral blood contains remarkably large quantities of viral particles (Beard, 1963). For this reason AMV was often used as a prototypic retrovirus in order to study viral assembly and later to produce large amounts of reverse transcriptase for both research and commercial purposes. Following the discovery of the v-src oncogene of RSV and the demonstration that it arose from the normal c-src proto-oncogene, a number of acute leukemia viruses were analysed by similar techniques and found to also contain viral oncogenes of cellular origin (Roussel et al., 1979). In the case of AMV, it was shown that almost the entire retroviral env gene had been replaced by a sequence of cellular origin (initially called mab or amv, but later renamed v-myb) (Duesberg et al., 1980; Souza et al., 1980). Remarkably, sequences contained in this myb oncogene were shared between AMV and the avian E26 leukemia virus, but were not contained in any other acutely transforming retroviruses. In addition, the E26 virus contained a second sequence of cellular origin (ets) that was unique. The E26 leukemia virus was first described in the 1960s and causes an acute erythroblastosis in chickens, more reminiscent of the disease caused by avian erythroblastosis virus (AEV) than by AMV (Ivanov et al., 1962).

摘要

禽成髓细胞瘤病毒(AMV)的v-myb癌基因在已知癌基因中独具特色,因为它在动物中仅引发急性白血病,且在培养中仅转化造血细胞。AMV于20世纪30年代被发现,是一种能在鸡身上引发类似人类急性髓性白血病疾病的病毒(霍尔等人,1941年)。这种禽逆转录病毒在癌症研究史上发挥了重要作用,原因有二。其一,AMV被用于证明并非所有致癌病毒都含有单一的致癌原理。具体而言,尽管劳氏肉瘤病毒(RSV)和AMV都能在胚胎成纤维细胞或造血细胞培养物中复制,但RSV只能转化成纤维细胞,而AMV只能转化造血细胞(巴卢达,1963年;德班和博伊蒂格,1981年a)。其二,感染AMV的鸡白细胞计数显著升高,因此其外周血中含有大量病毒颗粒(比尔德,1963年)。出于这个原因,AMV常被用作原型逆转录病毒,以研究病毒组装,后来还用于大量生产逆转录酶,用于研究和商业目的。在发现RSV的v-src癌基因并证明其源自正常的c-src原癌基因后,许多急性白血病病毒通过类似技术进行分析,发现也含有细胞起源的病毒癌基因(鲁塞尔等人,1979年)。就AMV而言,研究表明几乎整个逆转录病毒env基因已被细胞起源的序列取代(最初称为mab或amv,但后来重新命名为v-myb)(杜斯贝格等人,1980年;苏扎等人,1980年)。值得注意的是,这个myb癌基因包含的序列在AMV和禽E26白血病病毒之间共享,但在任何其他急性转化逆转录病毒中都不存在。此外,E26病毒含有第二个独特的细胞起源序列(ets)。E26白血病病毒于20世纪60年代首次被描述,可在鸡身上引发急性成红细胞增多症,这种疾病更类似于禽成红细胞增多症病毒(AEV)引发的疾病,而非AMV引发的疾病(伊万诺夫等人,1962年)。

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