Bos J L, Jochemsen A G, Bernards R, Schrier P I, van Ormondt H, van der Eb A J
Virology. 1983 Sep;129(2):393-400. doi: 10.1016/0042-6822(83)90178-2.
Plasmids containing the E1 region of Ad12 DNA can transform certain rodent cells into oncogenic cells. To study the role of the E1a subregion in the process of oncogenic transformation, Ad12 region E1 mutants carrying deletions in the E1a region were constructed. Deletion mutants pR7 and pR8 affect only the 13 S mRNA species encoded by region E1a, whereas deletion mutants pR11 and pR15 damage both the 12 S and 13 S E1a mRNA. All four mutants have lost their capacity to transform primary cultures of baby rat kidney cells, indicating that the E1a gene product encoded by 13 S mRNA is essential for transformation. It was further found that the mutated E1a regions of both pR7 and pR11 can induce expression of region E1b, which implies that the transformation deficiency of these mutants is not due to the inability to activate E1b expression. Surprisingly, the transforming capacity of pR7 and pR11 is restored when these mutant E1 regions are covalently coupled to the SV40 "enhancer" region. Cells transformed by these hybrids plasmids, however, were not tumorigenic in nude mice.
含有腺病毒12型（Ad12）DNA E1区的质粒可将某些啮齿动物细胞转化为致癌细胞。为了研究E1a亚区在致癌转化过程中的作用，构建了在E1a区带有缺失的Ad12 E1区突变体。缺失突变体pR7和pR8仅影响由E1a区编码的13S mRNA种类，而缺失突变体pR11和pR15则损害12S和13S E1a mRNA。所有这四个突变体均丧失了转化新生大鼠肾细胞原代培养物的能力，这表明由13S mRNA编码的E1a基因产物对于转化至关重要。进一步发现，pR7和pR11的突变E1a区均可诱导E1b区的表达，这意味着这些突变体的转化缺陷并非由于无法激活E1b表达所致。令人惊讶的是，当这些突变的E1区与SV40“增强子”区共价偶联时，pR7和pR11的转化能力得以恢复。然而，由这些杂种质粒转化的细胞在裸鼠中不具有致瘤性。
