TUMORIGENESIS BY MOUSE MAMMARY-TUMOR VIRUS - EVIDENCE FOR A COMMON REGION FOR PROVIRUS INTEGRATION IN MAMMARY-TUMORS

TUMORIGENESIS BY MOUSE MAMMARY-TUMOR VIRUS - EVIDENCE FOR A COMMON REGION FOR PROVIRUS INTEGRATION IN MAMMARY-TUMORS
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DOI:
10.1016/0092-8674(83)90418-x
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发表时间:
1983-01-01
期刊:
影响因子:
64.5
通讯作者:
DICKSON, C
DICKSON, C
中科院分区:
生物学1区
文献类型:
--
作者:
PETERS, G;BROOKES, S;DICKSON, C

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针对小鼠乳腺肿瘤病毒 (MMTV) 诱导的肿瘤中每个新整合的原病毒附近的独特序列细胞 DNA 制备了特异性探针。使用此类探针在BR6品系小鼠中筛选大量独立乳腺肿瘤表明,在迄今为止检查的40个肿瘤中,至少有17个肿瘤中,MMTV原病毒已整合到共同的染色体结构域中。从该区域分离出 10 公斤 (kb) 单拷贝 DNA 的 EcoRI 片段,并通过限制性内切酶图谱进行部分表征。位于不同肿瘤中该片段内的原病毒中,除了一个之外,所有原病毒都是完整的,方向相同,并且聚集在.apprx内。 3 kb 细胞 DNA。这些发现与 MMTV 肿瘤发生的插入诱变模型一致,其中原病毒在细胞 DNA 特定区域的整合可能会激活邻近的癌基因。这里描述的区域似乎与报道的 C3H 品系小鼠乳腺肿瘤区域不同。
Specific probes were prepared for unique-sequence cellular DNA adjacent to each of the newly integrated proviruses in tumors induced by mouse mammary tumor virus (MMTV). The use of such probes to screen a large number of independent mammary tumors in the BR6 strain of mouse has indicated that in at least 17 of the 40 tumors examined so far, an MMTV provirus has integrated into a common chromosomal domain. A 10 kilobage (kb) EcoRI fragment of single copy DNA from this region was isolated and partially characterized by restriction enzyme mapping. Of the proviruses located within this fragment in different tumors, all but one are complete, in the same orientation, and clustered within .apprx. 3 kb of cellular DNA. These findings are consistent with an insertional mutagenesis model for tumorigenesis by MMTV, in which the integration of a provirus in a particular region of cellular DNA may activate a neighboring oncogene. The region described here appears to be different from that reported for mammary tumors in the C3H strain of mouse.