Factors affecting the sensitivity of T-47D human breast cancer cells to tamoxifen.
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 G0-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. However, 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. These results illustrate that the conditions under which cells are cultured markedly affect their sensitivity to tamoxifen and highlight the need to specify these conditions when reporting effects of this drug.
D001943:Breast Neoplasms / Q000503:physiopathology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000633:toxicity*
D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol