Cancer is a consequence of the development of neoplastic cells which display altered regulation of differentiation and usually altered proliferative responses which is a consequence of the altered differentiation. A number of oncogenes have been defined as genes whose expression is essential for both initiation and maintenance of the neoplastic phenotype. The studies proposed here are focused on the mechanism by which one of the oncogenes, v-src, induces alteration of the differentiated state of infected target cells. The secondary aspect of the proposal is whether the action of the v-src oncogene is analogous to the function of the proto- oncogene c-src. Three approaches are proposed: (a) The potential role of receptors for extracellular matrix as targets for regulation by the src associated kinase will be examined. The test system employs a monoclonal antibody which can both block the fibronectin receptor and interrupt myogenic differentiation in a manner analogous to v- src. These studies will be extended in myogenesis, chondrogenesis and lens cell differentiation systems. (b) Viral constructs with different viral and cellular oncogenes will be used in conjunction with these differentiation systems to examine whether they affect differentiation by the same mechanism as v-src. And (c), the expression of homologues the viral oncogenes will be examined at specific stages of early development in the chicken embryo to explore their function in development.
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