Our laboratory studies the role of platelet-derived growth factor (PDGF) in the regulation of connective tissue cell division. During the early stages of our work, we demonstrated that PDGF does not function alone to regulate cell division; rather, a second set of growth factors contained within the platelet-poor plasma fraction of blood functioned synergistically with PDGF for the optimum growth response. We showed that PDGF and the plasma growth factors (identified later as EGF and the insulin-like growth factors) control sequential events in the cell cycle termed, respectively, """"""""competence"""""""" and """"""""progression."""""""" Our early studies culminated in the first purification of PDGF to homogeneity in 1979. More recently, we have focused on the molecular action of PDGF. Using somatic cell fusion techniques, we demonstrated a transcription-dependent event in the mitogenic response to PDGF. Using recombinant DNA technology, we isolated and characterized a new family of """"""""competence genes"""""""" whose transcription is stimulated by PDGF. Epidermal growth factor, insulin, and platelet-poor plasma have either weak or an undetectable effect on transcription of these genes. Overshadowing all these observations was the finding that a pair of oncogenes (c-myc and C-fas) are contained within the competence gene family. Using DNA-mediated transfection, we showed that during the next five years, we intend to deal with an unexplored area in PDGF molecular biology-- namely the regulation of gene expression by PDGF. We hope to define a promoter element on the competence genes that mediates their coordinate induction. Moreover, we hope to determine how the signal is transduced from the PDGF receptor to the chromatin. (N)
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