Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo
Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo
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DOI：
10.1073/pnas.200372597
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发表时间：
2000-10-10
影响因子：
11.1
通讯作者：
Lee, LA
中科院分区：
文献类型：
--
作者：
Kim, S;Li, Q;Lee, LA
C-Myc在永生化细胞中过表达可促进细胞增殖、抑制细胞分化、促进细胞转化。然而，最近的证据表明，当c-Myc在原代哺乳动物细胞中过度表达时，这些效应并不一定发生。我们试图通过重组腺病毒在小鼠肝脏中过表达人MYC来确定c-Myc在体内原代细胞中瞬时过表达的即时效应。小鼠静脉注射编码MYC的腺病毒(Ad/Myc)。E2F-1(Ad/E2F-1)，或β-半乳糖苷酶(Ad/LacZ)，注射后4d可检测到转基因表达。异位c-Myc的表达立即伴随着肝细胞的增大和变形，没有明显的细胞增殖或凋亡，这些结果在注射Ad/E2F-1或Ad/LacZ的小鼠的肝脏中不存在。明显的肝细胞核和核仁与大、小亚单位核糖体和核仁基因的上调有关，提示c-Myc可能诱导它们的表达以增加细胞质量。我们的研究支持c-Myc在体内控制脊椎动物细胞大小和代谢的作用，而不依赖于细胞的增殖。
Overexpression of c-Myc in immortalized cells increases cell proliferation, inhibits cell differentiation, and promotes cell transformation. Recent evidence suggests that these effects, however, do not necessarily occur when c-Myc is overexpressed in primary mammalian cells. We sought to determine the immediate effects of transient overexpression of c-Myc in primary cells in vivo by using recombinant adenovirus to overexpress human MYC in mouse liver. Mice were intravenously injected with adenoviruses encoding MYC(Ad/Myc). E2F-1 (Ad/E2F-1), or beta-galactosidase (Ad/LacZ), Transgene expression was detectable 4 days after injection. Expression of ectopic c-Myc was immediately accompanied by enlarged and dysmorphic hepatocytes in the absence of significant cell proliferation or apoptosis, These findings were not present in the livers of mice injected with Ad/E2F-1 or Ad/LacZ. Prominent hepatocyte nuclei and nucleoli were associated with the upregulation of large- and small-subunit ribosomal and nucleolar genes, suggesting that c-Myc may induce their expression to increase cell mass. Our studies support a role for c-Myc in the in vivo control of vertebrate cell size and metabolism independent of cell proliferation.