Wang J, Helin K, Jin P, Nadal-Ginard B
Department of Cardiology, Children's Hospital, Boston, Massachusetts 02135, USA.
Cell Growth Differ. 1995 Oct;6(10):1299-306.
Terminal differentiation of cultured myocytes requires withdrawal of the cells from the cell cycle. Constitutive overexpression of several oncogenes in myoblasts can inhibit in vitro myogenesis. Here we studied the role of the cellular transcription factor E2F1 on myogenic differentiation. E2F1 expression is irreversibly down-regulated during differentiation of C2C12 myocytes. Furthermore, deregulated E2F1 expression in C2C12 cells prevented myogenic differentiation. This inhibition of myogenesis was associated with the repression of myogenin expression and an elevated cyclin D1 expression. Moreover, E2F1-overexpressing myocytes failed to exit the cell cycle under differentiation conditions. These results are consistent with the notion that E2F1 can function as an oncogene and further suggest that E2F1 down-regulation is required for myogenic differentiation.
培养的肌细胞的终末分化需要使细胞退出细胞周期。成肌细胞中几种癌基因的组成型过表达可抑制体外成肌作用。在此，我们研究了细胞转录因子E2F1在肌源性分化中的作用。在C2C12肌细胞分化过程中，E2F1表达不可逆地下调。此外，C2C12细胞中E2F1表达失调会阻止肌源性分化。这种对成肌作用的抑制与肌细胞生成素表达的抑制和细胞周期蛋白D1表达的升高有关。此外，过表达E2F1的肌细胞在分化条件下未能退出细胞周期。这些结果与E2F1可作为癌基因发挥作用的观点一致，并进一步表明肌源性分化需要下调E2F1。
