Tsai K Y, Hu Y, Macleod K F, Crowley D, Yamasaki L, Jacks T
MIT Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Mol Cell. 1998 Sep;2(3):293-304. doi: 10.1016/s1097-2765(00)80274-9.
Mice mutant for the Rb tumor suppressor gene die in mid-gestation with defects in erythropoiesis, cell cycle control, and apoptosis. We show here that embryos mutant for both Rb and its downstream target E2f-1 demonstrate significant suppression of apoptosis and S phase entry in certain tissues compared to Rb mutants, implicating E2f-1 as a critical mediator of these effects. Up-regulation of the p53 pathway, required for cell death in these cells in Rb mutants, is also suppressed in the Rb/E2f-1 double mutants. However, double mutants have defects in cell cycle regulation and apoptosis in some tissues and die at approximately E17.0 with anemia and defective skeletal muscle and lung development, demonstrating that E2F-1 regulation is not the sole function of pRB in development.
视网膜母细胞瘤肿瘤抑制基因发生突变的小鼠在妊娠中期死亡，伴有红细胞生成、细胞周期控制和细胞凋亡缺陷。我们在此表明，与视网膜母细胞瘤突变体相比，视网膜母细胞瘤及其下游靶点E2f - 1均发生突变的胚胎在某些组织中表现出细胞凋亡和S期进入的显著抑制，这表明E2f - 1是这些效应的关键介质。视网膜母细胞瘤突变体中这些细胞死亡所需的p53通路的上调在视网膜母细胞瘤/E2f - 1双突变体中也受到抑制。然而，双突变体在某些组织的细胞周期调节和细胞凋亡方面存在缺陷，并在大约E17.0时死于贫血以及骨骼肌和肺部发育缺陷，这表明E2F - 1调节不是pRB在发育中的唯一功能。
