MANY TUMORS INDUCED BY THE MOUSE MAMMARY-TUMOR VIRUS CONTAIN A PROVIRUS INTEGRATED IN THE SAME REGION OF THE HOST GENOME
MANY TUMORS INDUCED BY THE MOUSE MAMMARY-TUMOR VIRUS CONTAIN A PROVIRUS INTEGRATED IN THE SAME REGION OF THE HOST GENOME
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DOI：
10.1016/0092-8674(82)90409-3
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发表时间：
1982-01-01
期刊：
影响因子：
64.5
通讯作者：
VARMUS, HE
中科院分区：
文献类型：
--
作者：
NUSSE, R;VARMUS, HE
小鼠乳腺肿瘤病毒（MMTV）是一种缓慢致瘤的逆转录病毒，其致瘤作用是否与宿主基因组某一区域的病毒DNA整合有关，本文对此进行了讨论。鉴定了一种携带一种新的MMTC原病毒的C3H小鼠乳腺肿瘤，并克隆到含有病毒和宿主序列连接的19千碱基DNA限制性片段。利用该克隆的宿主序列从正常小鼠DNA噬菌体文库中检索到25 kb的不间断位点（称为MMTV int1）。与MMTV int1亚克隆DNA片段杂交，检测到26例C3H乳腺肿瘤中18例DNA的酶切片段异常。这些重排似乎都是由于MMTV原病毒的插入，整合位点位于至少5个簇中，总距离为19 kb。在测试的少数肿瘤中发现了从int1转录的多腺苷化2.6 kb RNA，但在C3H小鼠的哺乳期乳腺中没有发现。在12个测试的病毒癌基因中，没有一个显示出与该位点克隆的DNA同源性。显然，在int1基因座内插入前病毒对MMTV的肿瘤发生非常有利，这可能是一种新的细胞癌基因表达增强的结果。
It was discussed as to whether oncogenesis by the mouse mammary tumor virus (MMTV), a slowly oncogenic retrovirus, involves integration of viral DNA within a certain region of the host genome. A C3H mouse mammary tumor bearing a single new MMTC provirus and cloned to 19 kilobase (kb) DNA restriction fragment containing a junction of viral and host sequences was identified. Host sequences from ths clone were used to retrieve 25 kb of the uninterrupted locus (termed MMTV int1) from a bacteriophage library of normal mouse DNA. Hybridization with subcloned DNA fragments of MMTV int1 detected abnormal restriction fragments in digests of DNA from 18 of 26 C3H mammary tumors. The rearrangements all appeared to be due to the insertion of an MMTV provirus, and the integration sites were located in at least 5 clusters over a total distance of 19 kb. A polyadenylated 2.6 kb RNA spp. transcribed from int1 was found in the few tumors tested, but not in lactating mammary glands from C3H mice. Of 12 tested viral oncogenes, none exhibited homology with cloned DNA from this locus. Evidently, tumorigenesis by MMTV is strongly favored by proviral insertion within the int1 locus, perhaps as a consequence of enhanced expression of a novel cellular oncogene.