Jin Guang, Tsuruyama Tatsuaki, Yamada Yoshihiro, Hiai Hiroshi
Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Cancer Sci. 2003 Sep;94(9):791-5. doi: 10.1111/j.1349-7006.2003.tb01520.x.
Spontaneous pre-B lymphomas in SL/Kh mice occur by somatic acquisition of a provirus genome of endogenous murine leukemia virus (MuLV). Inverse PCR amplification and sequence analyses of a provirus and its host flanking fragment revealed a proviral insertion into c-myc in 3 out of 60 SL/Kh pre-B lymphomas, named Svi3 lymphomas (SL/Kh virus integration site-3). Southern blot analysis revealed that two lymphomas had clonal integration in c-myc exon 1 and the other, in the promoter region. In 2 out of 3 Svi3 lymphomas, a fusion transcript of provirus 3' long terminal repeat and c-myc and a normal full-length c-myc transcript were obtained, but in one Svi3 lymphoma, only the normal transcript was obtained. All three Svi3 lymphomas had increased c-myc expression, producing normal 67-kDa c-Myc protein. Svi3 lymphomas had more mature phenotypes in the steps of early B-cell differentiation than Svi1 lymphomas, in which c-myc expression was indirectly up-regulated by provirus integration into Stat5a.
SL/Kh小鼠中的自发性前B淋巴瘤是通过体细胞获得内源性鼠白血病病毒(MuLV)的前病毒基因组而发生的。对一个前病毒及其宿主侧翼片段进行反向PCR扩增和序列分析发现,在60个SL/Kh前B淋巴瘤中有3个发生了前病毒插入c-myc基因,这些淋巴瘤被命名为Svi3淋巴瘤(SL/Kh病毒整合位点-3)。Southern印迹分析显示,其中两个淋巴瘤在c-myc外显子1中存在克隆性整合,另一个则在启动子区域。在3个Svi3淋巴瘤中的2个中,获得了前病毒3'长末端重复序列与c-myc的融合转录本以及正常的全长c-myc转录本,但在一个Svi3淋巴瘤中,只获得了正常转录本。所有3个Svi3淋巴瘤的c-myc表达均增加,产生正常的67 kDa c-Myc蛋白。与Svi1淋巴瘤相比,Svi3淋巴瘤在早期B细胞分化步骤中具有更成熟的表型,在Svi1淋巴瘤中,c-myc表达通过前病毒整合到Stat5a中而间接上调。