Borycki A G, Foucrier J, Saffar L, Leibovitch S A
Laboratoire de Cancérologie Expérimentale, UA1158, URA126 CNRS, Institut Gustave Roussy, Villejuif, France.
Oncogene. 1995 May 4;10(9):1799-811.
Colony Stimulating Factor (CSF-1) and the CSF-1 receptor (the c-fms product) are expressed during the proliferation of L6 alpha 1 rat myogenic cell line and both are down regulated during the formation of myotubes. In this study, we demonstrated that the expression of c-fms antisense RNA in stably transfected myoblasts repressed the CSF-1 receptor (c-fms protein) and induced a G1-growth arrest. Expression of the cyclin genes, that control passage through the G1 phase and in particular the cyclins identified as genes induced late in G1 by CSF-1 in mouse macrophages was studied in comparative Northern blot analyses of RNAs of subpopulations prepared by centrifugal elutriation of L6 alpha 1 myoblasts and induced Antifms D5 cells expressing c-fms antisense RNA. Repression of the CSF-1 receptor (c-fms product) did not affect cyclins A, B and G expression during the cell cycle. However, D-type cyclins and, at a lesser extend, cyclin E expression were dramatically altered specifically during the late G1 and early S phases, in Antifms D5 cells. These results suggest a role for the CSF-1/c-fms autocrine loop in the control of the proliferation of L6 alpha 1 rat myogenic cell line at the G1/S boundary via the D-type and E cyclins expression.
集落刺激因子（CSF-1）和CSF-1受体（c-fms产物）在L6α1大鼠成肌细胞系增殖过程中表达，而在肌管形成过程中二者均下调。在本研究中，我们证明稳定转染的成肌细胞中c-fms反义RNA的表达抑制了CSF-1受体（c-fms蛋白）并诱导了G1期生长停滞。在通过离心淘析L6α1成肌细胞制备的亚群RNA以及诱导表达c-fms反义RNA的抗fms D5细胞的比较Northern印迹分析中，研究了控制G1期进程的细胞周期蛋白基因的表达，特别是在小鼠巨噬细胞中被鉴定为CSF-1在G1期晚期诱导的基因的细胞周期蛋白。CSF-1受体（c-fms产物）的抑制在细胞周期中不影响细胞周期蛋白A、B和G的表达。然而，在抗fms D5细胞中，D型细胞周期蛋白以及程度较轻的细胞周期蛋白E的表达在G1期晚期和S期早期发生了显著改变。这些结果表明CSF-1/c-fms自分泌环通过D型和E型细胞周期蛋白的表达在L6α1大鼠成肌细胞系G1/S边界的增殖控制中发挥作用。
