Cook J L, Wilson B A, Wolf L A, Walker T A
Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Oncogene. 1993 Mar;8(3):625-35.
Ad2/5 E1A oncogene expression induces cytolytic susceptibility of rodent cells to natural killer lymphocytes. To determine whether the requisite thresholds of E1A oncoprotein expression differ for induction of cytolytic susceptibility as compared with other E1A-related activities, sarcoma cells expressing low or normal levels of E1A oncoproteins were compared for differences in morphological transformation, transactivation of viral genes, cytolytic susceptibility and tumorigenicity. Low-level E1A expression transformed sarcoma cells and transactivated the Ad5 E2A gene but did not induce the increased cytolytic susceptibility observed with normal levels of E1A expression. Furthermore, low-level E1A expressers retained the tumorigenicity of parental cells, whereas normal-level expressers were non-tumorigenic in hosts with intact natural killer (NK)-cell responses. In contrast to E1A, E1B oncogene expression caused no changes in morphological, cytolytic or tumorigenic phenotypes in these sarcoma cells. These data define an expression threshold for E1A-induced cytolytic susceptibility and associated NK-cell-dependent tumor rejection. The results suggest that the cellular mechanisms involved in E1A induction of cytolytic susceptibility differ from those involved in E1A-mediated cellular transformation and viral gene transactivation.
腺病毒2/5 E1A癌基因表达可诱导啮齿动物细胞对自然杀伤淋巴细胞产生溶细胞敏感性。为了确定与其他E1A相关活性相比，诱导溶细胞敏感性所需的E1A癌蛋白表达阈值是否不同，对表达低水平或正常水平E1A癌蛋白的肉瘤细胞在形态转化、病毒基因反式激活、溶细胞敏感性和致瘤性方面的差异进行了比较。低水平E1A表达可转化肉瘤细胞并反式激活腺病毒5 E2A基因，但不会诱导出正常水平E1A表达时所观察到的溶细胞敏感性增加。此外，低水平E1A表达细胞保留了亲代细胞的致瘤性，而正常水平表达细胞在具有完整自然杀伤（NK）细胞反应的宿主体内无致瘤性。与E1A相反，E1B癌基因表达在这些肉瘤细胞的形态学、溶细胞或致瘤表型上未引起变化。这些数据确定了E1A诱导溶细胞敏感性及相关NK细胞依赖性肿瘤排斥的表达阈值。结果表明，E1A诱导溶细胞敏感性所涉及的细胞机制不同于E1A介导的细胞转化和病毒基因反式激活所涉及的机制。
