RXR-ALPHA IS ESSENTIAL FOR MEDIATING THE ALL-TRANS-RETINOIC ACID-INDUCED GROWTH ARREST OF C2 MYOGENIC CELLS

In C2 muscle cells, retinoic acid (RA) induces growth arrest associate d with terminal differentiation. These RA actions are presumed to be m ediated through nuclear receptors (RARs and RXRs) that belong to the s uperfamily of ligand-dependent transcription factors, In this study, w e have characterized a myogenic C2 subclone, that unlike parental cell s, is resistant to growth inhibition and differentiation by RA, Examin ation 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 o f RXR alpha, we introduced an RXR alpha expression vector into RA-resi stant C2 cells by transient or stable transfections, Our results show that RXR alpha restores the response to RA in this subclone with respe ct to AP1 inhibition and growth arrest, These observations indicate th at RXR alpha plays a crucial role in mediating RA induced growth arres t of C2 myogenic cells.