Tumor-promoting activity of Epstein-Barr-virus-inducing factor transforming growth factor type beta (EIF/TGF-beta) is due to the induction of irreversible transformation

Abstract

EBV-inducing factor/transforming growth factor type beta (EIF/TGF-beta) exhibits tumor-promoting activity for C3H-10T1/2 mouse fibroblasts in vitro. Treatment of C3H 10 T 1/2 fibroblasts seeded at low density with initiating doses of UV light, followed by culture in the presence of EIF/TGF-beta leads to the appearance of foci of stably transformed cells that have the potential to grow in soft agar. The promoting effect depends both on the dose of EIF/TGF-beta applied and its continuous presence for 2 to 3 weeks. In addition to its procarcinogenic effect in tumor promotion, EIF/TGF-beta exhibits a strong negative effect on transformed cells surrounded by normal cells, indicating a dual role of EIF/TGF-beta in carcinogenesis. The lack of completely transformed individual cells in the initiated cell population and the negative effect of EIF/TGF-beta on transformed cells in contact with normal cells exclude any possible explanation of the tumor-promoting effect of EIF/TGF-beta as being the result of a selection process due to the establishment of growth advantages for cells transformed by the initiator. The data, in fact, indicate that tumor promotion by EIF/TGF-beta implies the stable acquisition of distinct qualitative changes by the cells.