DIFFERENTIATION OF HUMAN FIBROBLASTS TO TISSUE MACROPHAGES BY THE SNYDER-THEILEN FELINE SARCOMA-VIRUS IS ACCOMPANIED BY NUCLEAR ACCUMULATION OF THE TUMOR-SUPPRESSOR P53

Snyder-Theilen feline sarcoma virus (ST:FeSV)-transduced human fibrobl asts differentiate into tissue macrophages with many of the properties of normal macrophages. These cells express high levels of the gag-fes tyrosine kinase fusion protein, p85(v-fes), and exhibit an elevated l evel of tyrosine phosphorylation. Expression of the macrophage phenoty pe is accompanied by increased levels of DNA-binding activity and nucl ear accumulation of wild-type p53. The DNA-binding activity of the tra nscription factors Egr-1, CREB and Sp1, which are known to be involved in cell differentiation, is also increased in ST:FeSV-induced macroph ages. These observations suggest that v-fes can activate signal transd uction pathways normally involved in macrophage differentiation, and t hat transcription factors such as p53, further facilitate v-fes-induce d terminal differentiation.