Yang X H, Sladek T L
Department of Microbiology and Immunology, Finch University of Health Sciences, Chicago Medical School, IL 60064-3095, USA.
Gene Expr. 1995;4(4-5):195-204.
The E2F transcription factor can regulate expression of numerous cellular genes controlling proliferation, including proto-oncogenes and genes regulating cell cycle progression. Therefore, genes comprising the E2F gene family could potentially contribute to carcinogenesis. To test the potential of E2F to act as a transforming gene, a cDNA encoding E2F-1 was constitutively overexpressed in established rodent cells using a retroviral vector. Overexpressed E2F-1 was functional, as shown by stimulation of a transfected adenovirus E2 promoter driving a chloramphenicol acetyltransferase reporter gene in E2F-1 overexpressing cells. This stimulation was dependent on functional E2F binding sites in the promoter. Examination of phenotype showed that E2F-1 overexpression mediated cell transformation as measured by the ability of cells to form colonies in soft agar medium. In addition, overexpressed E2F-1 shortened the duration of the G1 cell cycle phase in proliferating cells, a property characteristic of other transforming genes. These data provide direct evidence that E2F-1 can act as a transforming gene and a critical regulator of cell cycle progression and suggest the possibility of E2F involvement in carcinogenesis.
E2F转录因子可调控众多控制细胞增殖的细胞基因的表达，包括原癌基因和调节细胞周期进程的基因。因此，E2F基因家族的基因可能在致癌过程中发挥作用。为了测试E2F作为转化基因的潜力，使用逆转录病毒载体在已建立的啮齿动物细胞中组成性过表达编码E2F-1的cDNA。过表达的E2F-1具有功能，这在过表达E2F-1的细胞中由驱动氯霉素乙酰转移酶报告基因的转染腺病毒E2启动子的刺激所证明。这种刺激依赖于启动子中的功能性E2F结合位点。表型检查表明，通过细胞在软琼脂培养基中形成集落的能力来衡量，E2F-1过表达介导了细胞转化。此外，过表达的E2F-1缩短了增殖细胞中G1细胞周期阶段的持续时间，这是其他转化基因的特性。这些数据提供了直接证据，表明E2F-1可以作为转化基因和细胞周期进程的关键调节因子，并提示E2F参与致癌作用的可能性。
