REPRESSION OF THE CSF-1 RECEPTOR (C-FMS PROTOONCOGENE PRODUCT) BY ANTISENSE TRANSFECTION INDUCES G1-GROWTH ARREST IN L6-ALPHA-1 RAT MYOBLASTS

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.