Rous sarcoma virus (RSV) has the ability to rapidly transform CEF. Transformation of committed cells generally leads to loss of differentiated cell functions and a convergence to a transformed phenotype. All the transforming variants of RSV carry the src gene. The src gene products has recently been identified as a phosphoprotein which may function as a kinase with specificity towards tyrosine. The src gene (V-oncogene) appears to be related to a gene found in the normal cell (c-oncogene), suggesting that oncogenesis secondary to retrovirus infections may be an aberration of (important) normal cell functions. We have observed that incubating RSV-transformed chicken embryo fibroblasts in vanadate (MuM) or retinoic acid (MuM) results in a significant modulation in the activity of the v-oncogene product, pp60src. We propose a series of studies in which the cellular and molecular effects of vanadate of retinoic acid will be studied.
The specific aims of this proposal are to examine pp60src isolated from treated transformed CEF for post-translational modifications, to identify and quantitate alteration changes in putative pp60src substrates under these conditions, and to correlate these changes with general characteristics associated with the transformed cell phenotype. These studies are directed toward a detailed understanding of tumorigenesis mediated by retroviruses (RSV) and chemotherapeutic modalities.
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