先前的動物模式研究顯示Rb蛋白被T121致癌基因抑制會導致小鼠腦上皮細胞不正常增殖及p53依賴性細胞凋亡。若使p53失活則導致快速腫瘤生長,因為細胞凋亡會減少85%。本研究分析T121E2F1-/-小鼠,發現E2F1的缺失可導致80%的細胞凋亡減少。此外,p53下游基因的轉譯在這個模式中也受到破壞,顯示E2F1應作用在p53的上游。然而,E2F1的缺失並不會使腫瘤加速生長,因為腫瘤細胞的增殖在E2F1缺失的情況下也被破壞了。由此可知,E2F1是腫瘤細胞增殖及進行p53依賴性細胞凋亡所同時必需的,這也解釋了為什麼E2F1在實驗系統中可同時身為致癌基因與抑癌基因的明顯矛盾。
Previous animal model studies have shown that inactivation of the Rb proteins in mouse brain epithelium by the T121 oncogene induces aberrant proliferation and p53-dependent apoptosis. p53 inactivation causes aggressive tumor growth due to an 85% reduction in apoptosis. In this study, by analyzing T121E2F1-/- mice, we found that E2F1 deficiency causes an 80% apoptosis reduction. In addition, transcriptional activation of p53 target genes is impaired in these mice, indicating that E2F1 acts upstream of p53. E2F1 deficiency does not accelerate tumor growth, however, because tumor cell proliferation is also impaired in the absence of E2F1. Thus, E2F1 is required both for tumor cell proliferation and p53-dependent apoptosis, explaining the apparent paradox that E2F1 can act as both an oncogene and a tumor suppressor in experimental systems.
