Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice
Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice
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DOI：
10.1128/jvi.71.1.9-16.1997
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发表时间：
1997-01-01
影响因子：
5.4
通讯作者：
Berns, A
中科院分区：
文献类型：
--
作者：
Scheijen, B;Jonkers, J;Berns, A
Moloney小鼠白血病病毒（MoMLV）在c-myc和Pim-1转基因小鼠中的插入突变允许鉴定在淋巴瘤发生中与转基因合作的癌基因，最近在MoMLV诱导的淋巴瘤中发现的常见插入位点pal-1位于发现几个独立整合簇的区域：is-1， gfi-1和evi-5。MoMLV在不同整合簇中的前病毒插入上调Gfi-1基因的转录活性，该基因位于pal-1位点。eis-1/pal-1/gfi-1/evi-5位点在E mu-myc转基因小鼠的b细胞前淋巴瘤（20%）以及H-2K-myc和E mu-pim-2转基因小鼠的t细胞淋巴瘤（75%）和E mu-pim-2（93%）中作为MoMLV前病毒插入的靶点。许多肿瘤既过表达Gfi-1，也过表达Myc和Pim基因家族成员，表明Gfi-1与Myc和Pim共同参与淋巴瘤的发生。然而，先前确定的插入位点bmi-1的前病毒整合与ei -1/pal-1/gfi-1/evi-5位点的整合是相互排斥的。这一发现提示Bmi-1和Gfi-1在淋巴细胞转化中属于同一补体群。
Insertional mutagenesis with Moloney murine leukemia virus (MoMLV) in c-myc and Pim-1 transgenic mice permits the identification of oncogenes that collaborate with the transgenes in lymphomagenesis, The recently identified common insertion site pal-1, in MoMLV-induced lymphomas, is located in a region in which several independent integration clusters are found: eis-1, gfi-1, and evi-5. Proviral insertions of MoMLV in the different integration clusters upregulate the transcriptional activity of the Gfi-1 gene, which is located within the pal-1 locus. The eis-1/pal-1/gfi-1/evi-5 locus serves as a target for MoMLV proviral insertions in pre-B-cell lymphomas of E mu-myc transgenic mice (20%) and in T-cell lymphomas of H-2K-myc (75%) and E mu-pim-2 (93%) transgenic mice. Many tumors overexpress both Gfi-1 as well as Myc and Pim gene family members, indicating that Gfi-1 collaborates with Myc and Pim in lymphomagenesis. Proviral integrations in the previously identified insertion site bmi-1 are, however, mutually exclusive with integrations in the eis-1/pal-1/gfi-1/evi-5 locus. This finding suggests that Bmi-1 and Gfi-1 belong to the same complementation group in lymphoid transformation.