Kim N K, Lee S H, Cha K Y, Seo J S
College of Medicine, Pochon CHA University, Kyonggi-do, Korea.
Mol Cells. 1998 Aug 31;8(4):383-7.
Simian virus 40 T-tumor antigen (SV40 T-ag) can induce a wide variety of tumors in hamsters and neonatal mice. These tumorigenic effects are predominantly due to the activity of early viral gene products, large T-antigen and small t-antigen. We have analyzed the expression of a DNA repair gene, N-methylpurine-DNA glycosylase (MPG), from different tissues of a non-transgenic (control) and SV40 T-ag expressing transgenic mice at the mRNA level. Expression of the transgene in thymus of adult mice was also detected by the presence of SV40 T-ag mRNA. Non-transgenic mice did not express the SV40 T-ag gene in their thymus, while the mRNA for MPG was found in thymus from both of transgenic and non-transgenic mice. The MPG gene was expressed in various tissues and is regulated in a tissue-specific manner. Northern blot analysis revealed that the transgenic mice showed considerably higher expression of MPG in the thymic carcinomas. The level of MPG mRNA in the thymic carcinoma was elevated about 5.7 fold, as compared with those found in the control thymus. MPG expression was significantly increased, either directly or indirectly, by the SV40 T-ag gene product. These findings provide the first in vivo observations that the SV40 T-ag gene induced thymic carcinomas associated with the activation of the DNA repair gene, MPG.
猿猴病毒40 T肿瘤抗原（SV40 T-ag）可在仓鼠和新生小鼠中诱发多种肿瘤。这些致瘤作用主要归因于早期病毒基因产物大T抗原和小t抗原的活性。我们已在mRNA水平分析了非转基因（对照）小鼠和表达SV40 T-ag的转基因小鼠不同组织中DNA修复基因N-甲基嘌呤-DNA糖基化酶（MPG）的表达。通过SV40 T-ag mRNA的存在也检测到了成年小鼠胸腺中转基因的表达。非转基因小鼠在其胸腺中不表达SV40 T-ag基因，而在转基因和非转基因小鼠的胸腺中均发现了MPG的mRNA。MPG基因在各种组织中表达，并以组织特异性方式受到调控。Northern印迹分析显示，转基因小鼠在胸腺癌中MPG的表达明显更高。与对照胸腺中的水平相比，胸腺癌中MPG mRNA的水平升高了约5.7倍。SV40 T-ag基因产物直接或间接显著增加了MPG的表达。这些发现首次在体内观察到SV40 T-ag基因诱发的胸腺癌与DNA修复基因MPG的激活有关。
