Lowther William, Wiley Korah, Smith Gilbert H, Callahan Robert
Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, Bethesda, MD 20892, USA.
J Virol. 2005 Aug;79(15):10093-6. doi: 10.1128/JVI.79.15.10093-10096.2005.
A novel common integration site for the mouse mammary tumor virus (MMTV) was identified (designated Int7) in five independently arising mouse mammary tumors. The insertion sites all cluster within a 1-kb region that is 2 to 3 kb 5' of the transcription initiation site of a gene, 2610028F08RIK, whose gene product contains furin-like and thrombospondin-like sequences. Expression of Int7 is normally very low or silent during various stages of mammary gland development, but MMTV integration at this site results in the activation of high steady-state levels of expression of the gene. These five tumors were also found to have two or three additional viral insertions, which in each case occurred flanking a member of either the Wnt and/or FGF gene family. Reverse transcriptase PCR results demonstrated that each of the viral insertions led to elevated expression of the presumed target flanking genes.
在五个独立发生的小鼠乳腺肿瘤中鉴定出一种新型的小鼠乳腺肿瘤病毒(MMTV)共同整合位点(命名为Int7)。插入位点均聚集在一个1 kb的区域内,该区域位于基因2610028F08RIK转录起始位点5'端2至3 kb处,其基因产物包含弗林蛋白酶样和血小板反应蛋白样序列。在乳腺发育的各个阶段,Int7的表达通常非常低或沉默,但MMTV在此位点的整合会导致该基因高稳态表达水平的激活。还发现这五个肿瘤有另外两个或三个病毒插入,在每种情况下,这些插入都发生在Wnt和/或FGF基因家族成员的侧翼。逆转录酶PCR结果表明,每个病毒插入都导致假定的侧翼靶基因表达升高。