Estradiol Stimulation and Inhibition of Cell Growth in New Estrogen-sensitive Cell Lines and Tumors Established from the MtTF4 Tumor1

Cell lines were established from the MtTF4 tumor, growth of which is inhibited by estradiol, in order to determine whether the effect observed in vivo was due to a direct action on tumor cells. Two different cell lines were obtained according to the medium in which tumor cells were dispersed and cultured. The F4P cells were obtained when the culture medium contained charcoal-treated fetal calf serum. The growth rate of these cells was slowed down by 17/3-estradiol in animals and also in culture during the early passages. Thereafter, they became insensitive to 17/3-estradiol in culture but remained negatively controlled in vivo. These cells, whatever their sensitivity to 170-estradiol, secrete proludili and carry functional I> dopamine binding sites. The F4Z cells were estab lished in medium containing fetal calf serum not treated with charcoal. The growth rate of these cells was stimulated by 17/3-estradiol in animals but was 17/8-estradiol insensitive in culture up to subculture 26. At this time, the growth rate of the subline also became stimulated by 17/-Õestradiol in culture, and this phenotype was still found at passage 108 (50% effective dose, 5 to 10 pmol; maximum stimulation, 180 to 300% of control). These cells neither secrete measurable amounts of prolactin nor have dopamine binding sites. Thus, according to the medium in which cells were dispersed and cultured, two different cell strains were derived from a tumor in which growth is inhibited by 17/3-estradiol. The point of interest is that the growth rate of one strain was inhibited by 17/3-estradiol, while the other was stimulated. Convergent data suggest that Mi 11 i tumor was hetero geneous and that selection had occurred during the dispersion or the culture of cells. Since the growth of one of these cell lines was slowed down transiently in culture we conclude that the inhibition of tumor growth could be due to a direct action of 17/8-estradiol on tumor cells. However, the dissociation between the response to 17/S-estradiol in culture and in the animal observed at some time of cell evolution suggests that environment affects the sensitivity of cells to 17/3-estradiol.