FACTORS AFFECTING THE SENSITIVITY OF T-47D HUMAN-BREAST CANCER-CELLS TO TAMOXIFEN

Abstract

Cell proliferation kinetics during growth of an estrogen receptor-positive human breast carcinoma cell line, T-47D, was defined, and some factors which modify its response to tamoxifen were investigated in vitro. T-47D cells were estrogen responsive when grown in charcoal-stripped fetal calf serum, but the addition of 17.beta.-estradiol did not fully restore the growth rate to that observed in the same concentration of fetal calf serum. Tamoxifen had both a low-dose, estrogen-reversible, growth-inhibitory effect and a high-dose, estrogen-irreversible, growth-inhibitory and cytotoxic effect on T-47D cells. Tamoxifen-induced growth inhibition was associated with a decrease in the percentage of S-phase cells and, to a lesser extent, G2-M-phase cells and an increase in Go-G1-phase cells. Plateau-phase cells were considerably less sensitive than were exponentially growing cells, and this was accompanied by a fall in unoccupied estrogen receptor content from 4407 .+-. 655 (S.E.) sites/cell in exponentially growing cultures to 1420 .+-. 315 sites/cell in plateau-phase cultures. T-47D cells were more sensitive to tamoxifen cytostasis when grown in fetal calf serum rather than charcoal-stripped fetal calf serum. With both types of growth medium, the sensitivity to tamoxifen was inversely related to the serum concentration, e.g., the 50%-inhibitory dose concentration increased 75-fold as the fetal calf serum concentration was increased from 0.25 to 10%. Addition of insulin to the culture medium had no effect on the growth rate, estrogen receptor content, or tamoxifen sensitivity of T-47D cells. The conditions under which cells are cultured markedly affect their sensitivity to tamoxifen. These conditions should be specified when reporting effects of this drug.