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 for 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 encoding 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 oligonucleotides, heparin, or suramin, indicating that enforced AIGF expression is responsible for the increase in DNA synthesis. However, A1 cells did not grow in serum-free medium unless stimulated with androgen. Recloning from A1 cells in semi-solid agar supplemented with fetal calf serum but without androgen quickly generated an autonomous subline that was able to grow rapidly in the serum-free medium irrespective of androgen stimulus. Mock-transfected SC-3 cells failed to form any colony under identical conditions. These results suggest that stable expression of AIGF alone is not sufficient for, but facilitates the conversion of SC-3 cells from androgen-dependent to -independent phenotype.