Isolation and characterization of a tamoxifen-resistant cell line derived from MCF-7 human breast cancer cells

Abstract

A tamoxifen-resistant variant (R27) was selected by cloning wild type MCF-7 cells. R27 has the same growth rate as MCF-7 under optimal conditions. But tamoxifen has no effect on the growth rate (growth constant of R27 under control condition, 0.071 +/- 0.007 day-1; tamoxifen-treated cells, 0.073 +/- 0.011 day-1) and minimal effects on thymidine incorporation in R27, whereas tamoxifen has a strongly suppressive effect on the growth rate and thymidine incorporation in MCF-7. The estradiol-mediated stimulation of growth in R27 is somewhat less than in MCF-7 (growth constants of R27 and MCF-7 are 0.112 +/- 0.015 and 0.125 +/- 0.009 day-1, respectively. R27 contains unoccupied receptors in both cytoplasmic and crude nuclear extract fractions with slightly higher numbers of cytosol receptors than wild type MCF-7. The same dissociation constant and the same molecular weight estimated by Sephadex chromatography and the same sucrose density behavior were observed in R27 and MCF-7. Extent of competition with estradiol and tamoxifen for cytoplasmic estrogen receptor is the same for R27 and MCF-7. Induction of progesterone receptor following treatment with estradiol is the same for R27 and MCF-7. Estrogen receptor is activated by salt and nucleotide in both MCF-7 and R27; however, the extent of activation is much higher in MCF-7 than R27.