Expression of the E6 and E7 genes of human papillomavirus (HPV16) extends the life span of human myoblasts
Expression of the E6 and E7 genes of human papillomavirus (HPV16) extends the life span of human myoblasts
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DOI：
10.1006/excr.1999.4407
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发表时间：
1999-04-10
影响因子：
3.7
通讯作者：
Shoubridge, EA
中科院分区：
文献类型：
--
作者：
Lochmüller, H;Johns, T;Shoubridge, EA
原代人成肌细胞（卫星细胞）与其他人细胞一样，在体外具有有限的寿命。在这里，我们表明，从人乳头瘤病毒16型的E6 E7早期区域的表达可以大大延长胎儿和卫星细胞衍生的成肌细胞的寿命，并释放他们从依赖生长因子通常需要他们的增殖。E6或E7基因的单独表达不足以赋予这种表型，尽管E7的表达确实延迟了细胞衰老。克隆培养物中E6 E7转录物的稳态水平与增殖能力相关，与分化成多核肌管的能力呈负相关。E7单独表达显着抑制成人和胎儿培养中的细胞融合。这些对成肌细胞分化的影响可能部分与E7的主要细胞靶点视网膜母细胞瘤蛋白（pRb）的水平有关。骨骼肌成肌细胞的终末分化与细胞周期的永久退出有关;然而，在分化的肌管中E6 E7的持续表达允许肌管细胞核响应于生长因子刺激重新进入S期。这些结果支持了一个关键的作用，pRb在收购和维护的分化状态在人类骨骼肌，并与p53，在控制增殖能力和响应外部生长因子。(C)北京：科学出版社.
Primary human myoblasts (satellite cells),like other human cells, have a limited life span in vitro. Here we show that expression of the E6E7 early region from human papillomavirus type 16 can greatly extend the life span of both fetal and satellite cell-derived myoblasts and release them from dependence on the growth factors normally necessary for their proliferation. Expression of either the E6 or the E7 gene alone was not sufficient to confer this phenotype, although expression of E7 did delay cellular senescence. The steady-state level of E6E7 transcripts in clonal cultures correlated with proliferative capacity and inversely with the capacity to differentiate into multinuclear myotubes. The expression of E7 alone markedly inhibited cell fusion in both adult and fetal cultures. These effects on myoblast differentiation could be related in part to the level of retinoblastoma protein (pRb), the major cellular target of E7. Terminal differentiation of skeletal myoblasts is associated with permanent withdrawal from the cell cycle; however, continued expression of E6E7 in differentiated myotubes permits reentry of myotube nuclei into S phase in response to growth factor stimulation. These results support a key role for pRb in the acquisition and maintenance of the differentiated state in human skeletal muscle and, in cooperation with p53, in the control of proliferative capacity and response to external growth factors. (C) 1999 Academic Press.