Fibroblast growth factor-8b-stimulated myogenic cell proliferation is suppressed by the promyelocytic leukemia gene

Muscle cell growth is regulated by growth-promoting and -inhibiting factors. In this study, the physiological effects of fibroblast growth factor (FGF)-8b and the promyelocytic leukemia (PML) gene on G8 myogenic cells were examined. FGF-8b was found to strongly stimulate myogenic cell proliferation. Signal transduction assays using AP-1/SEAP and E-box/SEAP reporters revealed that the transcriptional factors junB/c-fos and c-myc were involved in FGF-8b-stimulated G8 cell growth. Besides examining factors that positively stimulate myogenic cell growth, we also examined genes that negatively affect cell growth. PML is a growth suppressor gene and we studied its expression in G8 cells under different growth conditions. Immunohistochemical staining revealed that in the presence of low serum, PML was expressed in approximately 23.2% of all cultured G8 cells. However, under normal culture conditions (10% serum), PML expression dropped to about 2.6%. We found that the PML gene acted antagonistically to FGF-8b, as the overexpression of PML in G8 cells significantly inhibited FGF-8b-stimulated cell proliferation. It also inhibited AP-1 and E-box transactivation. However, we believe that PML functions as a stress-response gene in G8 cells rather than as a gene normally involved in regulating muscle development.