Hook L M, Agafonova Y, Ross S R, Turner S J, Golovkina T V
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
J Virol. 2000 Oct;74(19):8876-83. doi: 10.1128/jvi.74.19.8876-8883.2000.
Retroviruses are believed to induce tumors by acting as insertional mutagens that activate expression of cellular protooncogenes. Indeed, almost 90% of mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/He mice show upregulation of Int protooncogenes. We have analyzed three different MMTV variants [MMTV(C3H), MMTV(HeJ), and a genetically engineered MMTV hybrid provirus (HP)] for tumorigenicity in mice from two distinct genetic backgrounds. All three viruses were tumor causing in BALB/cJ mice. However, only MMTV(C3H), but not MMTV(HeJ) or HP, induced mammary tumors in C3H/He mice. All of the viruses were infectious on either background and up-regulated expression of Int genes in tumors they induced. Like HP, MMTV(HeJ) was found to be a genetic recombinant between endogenous Mtv1 provirus and exogenous MMTV(C3H). Sequence comparison of MMTV variants linked the tumorigenicity of MMTV(C3H) to the gag region of the retrovirus.
逆转录病毒被认为通过作为插入诱变剂来激活细胞原癌基因的表达从而诱发肿瘤。事实上,在C3H/He小鼠中,几乎90%的小鼠乳腺肿瘤病毒(MMTV)诱发的乳腺肿瘤显示Int原癌基因表达上调。我们分析了三种不同的MMTV变体[MMTV(C3H)、MMTV(HeJ)和一种基因工程MMTV杂交前病毒(HP)]在两种不同遗传背景小鼠中的致瘤性。所有三种病毒在BALB/cJ小鼠中都能致瘤。然而,只有MMTV(C3H),而不是MMTV(HeJ)或HP,能在C3H/He小鼠中诱发乳腺肿瘤。所有病毒在两种背景下都具有传染性,并且在它们诱发的肿瘤中上调Int基因的表达。与HP一样,MMTV(HeJ)被发现是内源性Mtv1前病毒和外源性MMTV(C3H)之间的基因重组体。MMTV变体的序列比较将MMTV(C3H)的致瘤性与逆转录病毒的gag区域联系起来。