We are studying the molecular mechanisms involved in the pathogenesis of rhabdomyosarcoma. This neoplasm probably arises due to a developmental disturbance during muscle formation. Since much has been learned recently about the molecular mechanisms underlying the commitment to muscle lineage and the mechanisms involved in normal muscle development, the study of rhabdomyosarcoma offers a unique opportunity to evaluate the relationship between differentiation arrest and the development of this pediatric embryonal tumor. For example, the activation of genes such as MyoD and myogenin have been shown to be required for the commitment of stem cells to myogenic differentiation. Additionally, several growth factors including TGF-beta and insulin-like growth factors have been implicated in the normal growth and maturation of muscle tissue. Our current focus has therefore bee aimed at identifying the roles that such growth factors and regulatory gene may play in the development of the striated muscle tumor, rhabdomyosarcoma. In particular we have focused on the role of insulin-like growth factor II in the development of this tumor since previous work has shown that this growth factor is expressed at abnormally high levels in these tumors compar to normal muscle. We have also been evaluating various agents in an attempt to in vitro differentiate tumor cell lines. These studies are aimed at identifying particular lesions within the normal differentiation pathway th may occur in the development of rhabdomyosarcoma. We are also using cDNA cloning approaches to identify potential molecular mechanisms which may distinguish between the unregulated continual growth of the embryonal tumor rhabdomyosarcoma, compared to the normal regulated growth of normal embryon human muscle.
