Gli1 expression in rhabdomyosarcoma cells

Sonic hedghog (Shh) singaling plays a critical role in organ development and its deregulation is associated with several tumors. Mutations or deletions of the Shh receptor Patched result in a constitutive activation of downstream signaling molecules, namely smoothened and the transcription factor Gli1. Mice with genetic alterations in the Shh pathway develop medulloblastoma and rhabdomyosracoma (RMS), indicating an important role of this pathway for the pathogenesis of RMS. We report here that expression of the protooncogen Gli1 correlates with the alveolar subtype of human rhabdomyosarcoma (RMS) cell lines. Gli1 expressing RMS cells are resistant against treatment with a specific inhibitor of smoothened, suggesting that Gli1 activation is independent from Shh-mediated patched activation. Ectopic expression of Gli1 or inhibition of Gli1 expression is asociated with altered phenotype and reduced growth of RMS cells. Thus, Gli1 may play a causative role in the formation of RMS and possibly provide a new molecular marker to distinguish RMS cells of the alveolar and embryonal subtyp.