The research in this proposal is intended to investigate the mechanism of transformation caused by the v-fms oncogene of the McDonough strain of feline sarcoma virus (SM-FeSV), and determine the role of the normal cell analogue in nonviral-induced tumors. Current evidence suggests that the v-fms transforming protein is functioning in some respects as a growth factor receptor. This implies that the protein product of the normal cellular c-fms proto-oncogene also may function as a growth factor receptor and that alterations in the expression of this protein could result in neoplastic transformation. To investigate these possibilities, a combination of molecular biology and cell biology techniques will be used to define the segments of the v-fms proteins necessary for transformation and determine how that relates to the potential function of this protein as a growth factor receptor. These studies should indicate specific mechanisms in transformation and clarify the molecular events that control normal cell growth. In addition, antibodies will be produced to the c-fms protein by cloning exons of c-fms and expressing these as fusion proteins using trpE expression vectors. This will allow the identification and characterization of the c-fms protein in both normal and tumor tissue. Finally, the expression of the c-fms protein in human tumors will be studied and model systems will be established for determining whether tumor cells expressing the c-fms protein can be killed or transformation suppressed by immunotherapy with anti-fms antibodies. These studies have a direct and obvious health relatedness and it is hoped that they will form the basis for future research on specific human tumors.
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