Cohen J C, Varmus H E
J Virol. 1980 Aug;35(2):298-305. doi: 10.1128/JVI.35.2.298-305.1980.
We analyzed two experimental situations to assess the role of endogenous mouse mammary tumor virus (MMTV) DNA in the genesis of mammary carcinomas. (i) GR mice carry in their germ line one or more proviruses indistinguishable by limited restriction mapping from the proviruses introduced into cells by experimental infection with the highly tumorigenic virus isolated from GR mouse milk, MMTV(GR). Most tumors arising in GR mice contain one or more proviruses at various sites in tumor DNA in addition to those present endogenously. Detection of these new proviruses is possible as a consequence of the clonal or quasiclonal character of the tumors. (ii) C3H/He mice carry three units of endogenous viral DNA, none of which resembles the DNA of the commonly encountered strains of milk-borne MMTV. Nevertheless, MMTV-associated tumors arise late in life when these animals are removed from the influence of milk-borne virus; the responsible agent, MMTV(C3Hf), can also produce tumors in BALB/c mice. We found that tumors arising in both C3Hf/He mice and BALB/c mice infected with MMTV(C3Hf) were clonal or quasiclonal and contained one or more new copies of proviral DNA at various sites in the host genome. These new proviruses were readily distinguished from the proviruses of the common milk-borne virus strains and closely resembled unit II of endogenous MMTV DNA (Cohen et al., J. Virol., 32:483-496). Thus, in both experimental systems, we found evidence for new proviruses in mammary tumors, despite the preexistence of similar or identical proviruses in the germ line. The results suggest that the repositioning of MMTV proviruses may be required for the full expression of the oncogenic potential of endogenous MMTV DNA.
我们分析了两种实验情况，以评估内源性小鼠乳腺肿瘤病毒（MMTV）DNA在乳腺癌发生过程中的作用。（i）GR小鼠在其种系中携带一种或多种前病毒，通过有限的限制性图谱分析，这些前病毒与通过实验感染从GR小鼠乳汁中分离出的高致瘤性病毒MMTV(GR)导入细胞的前病毒无法区分。除了内源性存在的那些前病毒外，GR小鼠中出现的大多数肿瘤在肿瘤DNA的不同位点还含有一种或多种前病毒。由于肿瘤的克隆或准克隆特性，这些新前病毒是可以检测到的。（ii）C3H/He小鼠携带三个内源性病毒DNA单位，其中没有一个与常见的乳汁传播的MMTV菌株的DNA相似。然而，当这些动物不再受乳汁传播病毒的影响时，MMTV相关肿瘤在其生命后期出现；致病因子MMTV(C3Hf)也能在BALB/c小鼠中产生肿瘤。我们发现，感染MMTV(C3Hf)的C3Hf/He小鼠和BALB/c小鼠中出现的肿瘤都是克隆性或准克隆性的，并且在宿主基因组的不同位点含有一个或多个前病毒DNA的新拷贝。这些新前病毒很容易与常见的乳汁传播病毒株的前病毒区分开来，并且与内源性MMTV DNA的单位II非常相似（Cohen等人，《病毒学杂志》，32:483 - 496）。因此，在这两个实验系统中，尽管种系中已经存在相似或相同的前病毒，我们还是在乳腺肿瘤中发现了新前病毒的证据。结果表明，MMTV前病毒的重新定位可能是内源性MMTV DNA致癌潜力充分表达所必需的。
