Stanelle Jens, Stiewe Thorsten, Theseling Carmen C, Peter Martin, Pützer Brigitte M
Centre for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen, Medical School, Hufelandstrasse 55, D-45122 Essen, Germany.
Nucleic Acids Res. 2002 Apr 15;30(8):1859-67. doi: 10.1093/nar/30.8.1859.
The p16/RB/E2F regulatory pathway, which controls transit through the G1 restriction point of the cell cycle, is one of the most frequent targets of genetic alterations in human cancer. Any of these alterations results in the deregulated expression of the transcription factor E2F, one of the key mediators of cell cycle progression. Under these conditions, E2F1 also participates in the induction of apoptosis by a p53-dependent pathway, and independently of p53. Recently, we identified the p53-homolog p73 as a first direct target of p53-independent apoptosis. Here, we used a cDNA microarray to screen an inducible E2F1-expressing Saos-2 cell line for E2F1 target genes. Expression analysis by cDNA microarray and RT-PCR revealed novel E2F1 target genes involved in E2F1-regulated cellular functions such as cell cycle control, DNA replication and apoptosis. In addition, the identification of novel E2F1 target genes participating in the processes of angiogenesis, invasion and metastasis supports the view that E2F1 plays a central role in many aspects of cancer development. These results provide new insight into the role of E2F1 in tumorigenesis as a basis for the development of novel anti-cancer therapeutics.
p16/RB/E2F调控通路控制细胞周期通过G1限制点，是人类癌症中最常见的基因改变靶点之一。这些改变中的任何一种都会导致转录因子E2F表达失调，E2F是细胞周期进程的关键调节因子之一。在这些情况下，E2F1还通过p53依赖的途径并独立于p53参与凋亡诱导。最近，我们鉴定出p53同源物p73是p53非依赖凋亡的首个直接靶点。在此，我们使用cDNA微阵列筛选可诱导表达E2F1的Saos-2细胞系中的E2F1靶基因。通过cDNA微阵列和RT-PCR进行的表达分析揭示了参与E2F1调控的细胞功能（如细胞周期控制、DNA复制和凋亡）的新E2F1靶基因。此外，对参与血管生成、侵袭和转移过程的新E2F1靶基因的鉴定支持了E2F1在癌症发展的许多方面起核心作用的观点。这些结果为E2F1在肿瘤发生中的作用提供了新的见解，作为开发新型抗癌疗法的基础。
