Hunt K K, Deng J, Liu T J, Wilson-Heiner M, Swisher S G, Clayman G, Hung M C
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1997 Nov 1;57(21):4722-6.
Apoptosis is a mode of cell death that is carefully regulated based on cellular and environmental signals. The ability to modulate the individual cellular machinery and thereby to promote apoptosis is an important strategy in cancer therapy. It has previously been shown that overexpression of the transcription factor E2F-1 can induce apoptosis in quiescent rat embryo fibroblasts. This effect has been reported to occur in a p53-dependent manner. To investigate whether overexpression of E2F-1 could also induce apoptosis in human cancer cells, a recombinant adenovirus vector containing the transgene E2F-1 under control of the cytomegalovirus promoter (Ad5CMVE2F) was used to induce high levels of the E2F-1 protein in human breast and ovarian carcinoma cell lines. Significant morphological changes occurred in four of the five cell lines within 48 h of transduction with the Ad5CMVE2F. These changes were consistent with apoptosis, which was confirmed further by DNA fragmentation assay and fluorescence-activated cell sorting analysis. On the basis of these assays, which show that apoptosis occurred in those cell lines with mutations in the p53 gene, we suggest that the induction of E2F-1-mediated apoptosis does not require wild-type p53 when E2F-1 is overexpressed using an adenovirus-based strategy.
细胞凋亡是一种基于细胞和环境信号而受到严格调控的细胞死亡方式。调节个体细胞机制从而促进细胞凋亡的能力是癌症治疗中的一项重要策略。先前的研究表明，转录因子E2F-1的过表达可诱导静止的大鼠胚胎成纤维细胞发生凋亡。据报道，这种效应是以p53依赖的方式发生的。为了研究E2F-1的过表达是否也能诱导人类癌细胞凋亡，一种重组腺病毒载体被用于在人乳腺癌和卵巢癌细胞系中诱导高水平的E2F-1蛋白表达，该载体含有在巨细胞病毒启动子控制下的转基因E2F-1（Ad5CMVE2F）。在用Ad5CMVE2F转导后的48小时内，五个细胞系中的四个出现了显著的形态学变化。这些变化与细胞凋亡一致，DNA片段化分析和荧光激活细胞分选分析进一步证实了这一点。基于这些显示p53基因发生突变的细胞系中出现细胞凋亡的检测，我们认为，当使用基于腺病毒的策略使E2F-1过表达时，E2F-1介导的细胞凋亡的诱导不需要野生型p53。
