One crucial way in which tumor cells differ from their normal cellular counterparts is in their ability to grow independently of growth factors. These growth factors, their concentrations and availability, provide a means for the organism to control the growth of its component cells. Tumor cells, by no longer requiring growth factors, are thus able to proliferate without control, having escaped normal constraints on growth. The same transforming oncogene (v-ras) will rapidly render cells of very different lineages independent of their respective growth factors. For example, fibroblasts become independent of platelet-derived growth factor, endothelial cells independent of endothelial cell growth factor, mast cells independent of interleukin 3, and B and T lymphocytes independent of antigen/BSF-1 and antigen/IL-2, respectively. The mechanisms by which transformed cells become autonomous of growth factors are not entirely clear, but it is apparent that this independence is critical to the unchecked growth of the tumor. A recent discovery is that certain viral oncogenes control the expression of growth-related proto-oncogenes in the host cell. It is hypothesized that this activity may be related to the ability of the viral oncogene to render the infected cells independent of the need for growth factors. Furthermore, this activity of the oncogenes allows creation of viable cellular """"""""mutants"""""""" with blocks in growth factor signal transduction, providing a powerful tool to the study of growth factor action in normal and transformed cells. The approach proposed then is to use this action of viral oncogenes to begin to dissect out the element sof at least one important and common growth factor signal transduction is intrinsic to the oncogenic activities of v-ras and other viral oncogenes. Finally, this system will be used to explore the more complex growth factor, lymphokine and antigen interactions with lymphoid cells, and the way in which these growth factor requirements and responses change after transformation.
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