Yanagawa S, Kakimi K, Tanaka H, Murakami A, Nakagawa Y, Kubo Y, Yamada Y, Hiai H, Kuribayashi K, Masuda T
Department of Viral Oncology, Faculty of Medicine, Kyoto University, Japan.
J Virol. 1993 Jan;67(1):112-8. doi: 10.1128/JVI.67.1.112-118.1993.
Mouse mammary tumor virus (MMTV) is a slowly transforming retrovirus associated primarily with the induction of mammary tumors. It is widely accepted that T-cell lymphomas of various mouse strains are associated with extra proviruses of MMTV. These extra proviruses showed site-specific rearrangements in the U3 region of long terminal repeats (LTRs), consisting of about 400 nucleotide deletions and occasional substitution resulting in unique tandem repeats. However, the question of whether these mutant MMTVs cause lymphomas has not been experimentally resolved. Here we present distinct evidence that they do. We constructed chimeric MMTVs by replacing the LTR of the recently constructed pathogenic MMTV provirus clone with rearranged LTRs of MMTV proviruses obtained from two DBA/2 mouse lymphoma cell lines, MLA and DL-8, and inoculated them into BALB/c mice. These mice developed lymphomas, but no mammary tumors, 4 to 11 months postinoculation, whereas the original pathogenic MMTV clone alone induced mammary tumors. These results showed that the tissue specificity of MMTV tumorigenesis is determined by the LTR structures.
小鼠乳腺肿瘤病毒（MMTV）是一种主要与乳腺肿瘤诱导相关的缓慢转化逆转录病毒。人们普遍认为，各种小鼠品系的T细胞淋巴瘤与MMTV的额外前病毒有关。这些额外的前病毒在长末端重复序列（LTR）的U3区域显示出位点特异性重排，包括约400个核苷酸的缺失和偶尔的替换，从而产生独特的串联重复序列。然而，这些突变的MMTV是否会导致淋巴瘤的问题尚未通过实验得到解决。在此，我们提供了明确的证据表明它们会导致淋巴瘤。我们通过用从两个DBA/2小鼠淋巴瘤细胞系MLA和DL-8获得的MMTV前病毒的重排LTR替换最近构建的致病性MMTV前病毒克隆的LTR，构建了嵌合MMTV，并将它们接种到BALB/c小鼠体内。接种后4至11个月，这些小鼠发生了淋巴瘤，但没有乳腺肿瘤，而单独的原始致病性MMTV克隆诱导了乳腺肿瘤。这些结果表明，MMTV致瘤的组织特异性由LTR结构决定。
