Bouvard V, Matlashewski G, Gu Z M, Storey A, Banks L
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Virology. 1994 Aug 15;203(1):73-80. doi: 10.1006/viro.1994.1456.
The E5 gene from HPV-16 has recently been shown to stimulate anchorage-independent growth of murine 3T3 cells and this phenotype was enhanced in the presence of epidermal growth factor (EGF). Since EGF is capable of stimulating cellular signal transduction, we have compared levels of EGF-induced c-fos and c-jun mRNA in E5-expressing 3T3 cells. We present data showing that the expression of c-fos and c-jun was higher in E5-expressing 3T3 cells than in control cells. Complexes of c-fos/c-jun constitute the AP1 transcription factor and the HPV-16 promoter/enhancer contains AP1 enhancer elements. HPV-16 promoter activity was therefore examined in cells transfected with the E5 gene and data are presented which reveal that the viral enhancer is more active in E5-expressing cells. Since the viral E7 gene product has been shown to cooperate with v-fos and certain growth factors for transformation and stimulation of DNA synthesis, we investigated the possible cooperation between E5 and E7 to induce cell proliferation. Transfection of E5 and E7 genes into primary rodent epithelial cells produced a potent mitogenic response which was enhanced in the presence of EGF. These results suggest that E5 may cooperate with the E7 gene to stimulate cell proliferation in vivo.
最近研究表明，人乳头瘤病毒16型（HPV-16）的E5基因可刺激鼠3T3细胞进行不依赖贴壁的生长，并且在表皮生长因子（EGF）存在的情况下，这种表型会增强。由于EGF能够刺激细胞信号转导，因此我们比较了在表达E5的3T3细胞中EGF诱导的c-fos和c-jun mRNA的水平。我们提供的数据表明，表达E5的3T3细胞中c-fos和c-jun的表达高于对照细胞。c-fos/c-jun复合物构成AP1转录因子，而HPV-16启动子/增强子含有AP1增强子元件。因此，我们检测了转染E5基因的细胞中HPV-16启动子的活性，并提供的数据显示病毒增强子在表达E5的细胞中更具活性。由于病毒E7基因产物已被证明可与v-fos和某些生长因子协同作用，以促进转化和刺激DNA合成，因此我们研究了E5和E7之间可能存在的协同作用，以诱导细胞增殖。将E5和E7基因转染到原代啮齿动物上皮细胞中可产生强烈的促有丝分裂反应，并且在EGF存在的情况下会增强。这些结果表明，E5可能与E7基因协同作用，在体内刺激细胞增殖。
