FACILITATION OF AUTONOMOUS PHENOTYPE ACQUISITION IN ANDROGEN-DEPENDENT SHIONOGI CARCINOMA-115 CELLS BY TRANSFECTION OF ANDROGEN-INDUCED GROWTH-FACTOR EXPRESSION VECTOR

Androgen-induced growth factor (AIGF) is an autocrine growth factor fo r androgen-dependent SC-3 cells, which is induced by androgen stimuli. To elucidate the mechanism of the progression from hormone-dependent to -independent tumor, we transfected an expression vector of cDNA enc oding AIGF into SC-3 cells and established a stable transfectant (A1) expressing AIGF. A1 cells showed enhanced DNA synthesis. This enhanced DNA synthesis was blocked by exposing the cells to AIGF antisense oli gonucleotides, heparin, or suramin, indicating that enforced AIGF expr ession is responsible for the increase in DNA synthesis. However, A1 c ells did not grow in serum-free medium unless stimulated with androgen . Recloning from A1 cells in semi-solid agar supplemented with fetal c alf serum but without androgen quickly generated an autonomous subline that was able to grow rapidly in the serum-free medium irrespective o f androgen stimulus. Mock-transfected SC-3 cells failed to form any co lony under identical conditions. These results suggest that stable exp ression of AIGF alone is not sufficient for, but facilitates the conve rsion of SC-3 cells from androgen-dependent to -independent phenotype.