In C2 muscle cells, retinoic acid (RA) induces growth arrest associated with terminal differentiation. These RA actions are presumed to be mediated through nuclear receptors (RARs and RXRs) that belong to the superfamily of ligand-dependent transcription factors. In this study, we have characterized a myogenic C2 subclone, that unlike parental cells, is resistant to growth inhibition and differentiation by RA. Examination of these RA-sensitive and resistant C2 cells for the expression of retinoid acid receptors revealed a lack of RXR alpha expression at the myoblast stage in resistant C2 cells. To determine the functions of RXR alpha, we introduced an RXR alpha expression vector into RA-resistant C2 cells by transient or stable transfections. Our results show that RXR alpha restores the response to RA in this subclone with respect to AP1 inhibition and growth arrest. These observations indicate that RXR alpha plays a crucial role in mediating RA induced growth arrest of C2 myogenic cells.
Cell Differentiation Cell Division