Participation of small GTPases Rac1 and Cdc42Hs in myoblast transformation
Participation of small GTPases Rac1 and Cdc42Hs in myoblast transformation
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DOI：
10.1038/sj.onc.1205396
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发表时间：
2002-04-25
期刊：
影响因子：
8
通讯作者：
Gauthier-Rouvière, C
中科院分区：
文献类型：
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作者：
Meriane, M;Charrasse, S;Gauthier-Rouvière, C
我们以前已经表明，活性Rac1和Cdc4Hs的表达抑制骨骼肌细胞分化。我们在这里表明，溴脱氧尿苷掺入和细胞周期蛋白D1的表达，活性Rac1和Cdc42Hs的表达，但不RhoA损害细胞周期退出分化培养基中培养的L6成肌细胞。此外，表达活化形式的Rac1和Cdc42Hs elaborate的细胞接触抑制和锚定依赖性生长的损失，所测量的焦点形成活性和生长在软琼脂。再次发现RhoA没有这种效果。我们在三个人横纹肌肉瘤衍生的细胞系中发现了组成性Rac1和Cdc42Hs激活，这是儿童时期肌肉前体产生实体瘤的最常见原因之一。最后，显性负性形式的Rac 1和Cdc42 H抑制RD横纹肌肉瘤细胞系的细胞增殖。这些数据表明小GTP酶Rac 1和Cdc42Hs在骨骼肌肿瘤的产生中起重要作用。
We have previously shown that expression of active Rac1 and Cdc4Hs inhibits skeletal muscle cell differentiation. We show here, by bromodeoxyuridine incorporation and cyclin D1 expression, that the expression of active Rac1 and Cdc42Hs but not RhoA impairs cell cycle exit of L6 myoblasts cultured in differentiation medium. Furthermore, expression of activated forms of Rac1 and Cdc42Hs elicits the loss of cell contact inhibition and anchorage-dependent growth as measured by focus forming activity and growth in soft agar. RhoA was once again not found to have this effect. We found a constitutive Rac1 and Cdc42Hs activation in three human rhabdomyosarcoma-derived cell lines, one of the most common causes of solid tumours arising from muscle precursors during childhood. Finally, dominant negative forms of Rac1 and Cdc42Hs inhibit cell proliferation of the RD rhabdomyosarcoma cell line. These data suggest an important role for the small GTPases Rac1 and Cdc42Hs in the generation of skeletal muscle tumours.