CHARACTERIZATION OF GROWTH-FACTOR RESPONSIVENESS AND ALTERATIONS IN GROWTH-FACTOR HOMEOSTASIS INVOLVED IN THE TUMORIGENIC CONVERSION OF MOUSE OVAL CELLS

Five mouse oval cell lines were investigated in regards to their growt h and differentiation factor (GDF) responsiveness and to changes in th eir GDF responsiveness following tumorigenic conversion. In all 59 GDF s and 11 comitogens were evaluated with variable responsiveness, depen ding on the mouse oval cell line under study, observed. Analysis of ov al cell GDF responsiveness during tumorigenic conversion revealed that tumorigenic variants displayed alterations in GDF responsiveness whic h correlated with tumorigenicity. In addition, analysis of autocrine/p aracrine growth factor production demonstrates that most tumorigenic v ariants produce growth factors. These studies demonstrate for the firs t time that (1) mouse oval cells respond to a wide variety of GDFs inc luding various members of the interleukin, chemokine, stem cell factor , EGF, FGF, PDGF, TGF-beta, VEGF, insulin, CSF, TNF, HGF, and IFN grow th and differentiation factor families in addition to multiple comitog ens and (2) during tumorigenic conversion mouse oval cells undergo alt erations which result in both alterations in GDF responsiveness and th e autocrine/paracrine production of multiple GDFs.