Pim D, Collins M, Banks L
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Oncogene. 1992 Jan;7(1):27-32.
We have until recently made several unsuccessful attempts to assign any activity to the human papillomavirus type 16 (HPV-16) E5 gene product. However, studies with the bovine papilloma virus 1 (BPV-1) E5 protein indicated an interaction with the epidermal growth factor receptor (EGFR). In light of the overall similarity between the HPV and BPV E5 proteins we attempted to determine whether the HPV-16 E5 gene had any common activity. In cells expressing high levels of EGFR plus HPV-16 E5 we found a dramatically increased proliferative activity in soft-agar assays in the presence of EGF. The specificity of this activity was monitored by the addition of other mitogenic agents. The phorbol ester phorbol 12-myristate 13-acetate (PMA) had no effect on the E5-containing cells, although insulin weakly stimulated their growth in soft agar. Further analysis revealed the same number of EGF receptors were present on the E5-containing cells as on the control cells, although the E5 cells were more sensitive to lower concentrations of EGF. These results imply that E5 is amplifying the mitogenic signals from the EGFR in an as yet unknown manner, but which may form the basis of interactions with a variety of growth factor receptors. This report brings to three the number of transforming genes encoded by HPV-16.
直到最近，我们对人乳头瘤病毒16型（HPV - 16）E5基因产物进行了几次无果的活性测定尝试。然而，对牛乳头瘤病毒1型（BPV - 1）E5蛋白的研究表明，它与表皮生长因子受体（EGFR）存在相互作用。鉴于HPV和BPV E5蛋白之间的总体相似性，我们试图确定HPV - 16 E5基因是否具有任何共同活性。在表达高水平EGFR和HPV - 16 E5的细胞中，我们发现在存在表皮生长因子（EGF）的情况下，软琼脂试验中的增殖活性显著增加。通过添加其他促有丝分裂剂来监测这种活性的特异性。佛波酯佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）对含E5的细胞没有影响，尽管胰岛素在软琼脂中对它们的生长有微弱刺激作用。进一步分析表明，含E5的细胞上存在的EGF受体数量与对照细胞相同，尽管E5细胞对较低浓度的EGF更敏感。这些结果表明，E5正以一种尚不清楚的方式放大来自EGFR的促有丝分裂信号，但这可能构成与多种生长因子受体相互作用的基础。本报告使HPV - 16编码的转化基因数量增加到三个。
