Gelly C, Pasqualini J R
C.N.R.S. Steroid Hormone Research Unit, Foundation for Hormone Research, Paris, France.
J Steroid Biochem. 1988;30(1-6):321-4. doi: 10.1016/0022-4731(88)90115-x.
R-27 cells, a tamoxifen-resistant clone of MCF-7 mammary cancer cells, were used to study the effect of tamoxifen and its derivatives (4-hydroxytamoxifen, N-desmethyltamoxifen and cis-tamoxifen) on the conversion of estrone sulfate to estradiol. The present data indicate that (1) tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and cis-tamoxifen inhibit the uptake of the radioactivity after incubation of these triphenylethylene derivatives with [3H]-estrone sulfate; (2) there is a significant decrease of the conversion of estrone sulfate to estradiol by these antiestrogens; (3) the concentrations of estradiol (cytosol + 0.6 M KCl nuclear extract) which are 293 +/- 50 pg/mg DNA in the control studies (estrone sulfate alone), diminish to 26 +/- 5 pg/mg DNA after addition of tamoxifen, to 9 +/- 2 with 4-hydroxytamoxifen, to 24 +/- 7 with N-desmethyltamoxifen and to 32 +/- 6 with cis-tamoxifen. It is concluded that estrone sulfate can play an important role in the biological responses to estrogens in this breast cancer cell line and tamoxifen and its derivatives block the conversion of estrone sulfate to estradiol. The decrease in concentration of estradiol could be explained by the presence of the estrogen receptor system but other ways of the action of antiestrogens remain to be explored.
R-27细胞是MCF-7乳腺癌细胞的他莫昔芬耐药克隆，用于研究他莫昔芬及其衍生物（4-羟基他莫昔芬、N-去甲基他莫昔芬和顺式他莫昔芬）对硫酸雌酮转化为雌二醇的影响。目前的数据表明：（1）他莫昔芬、4-羟基他莫昔芬、N-去甲基他莫昔芬和顺式他莫昔芬在与[3H]-硫酸雌酮孵育后，会抑制放射性物质的摄取；（2）这些抗雌激素药物会使硫酸雌酮向雌二醇的转化显著减少；（3）在对照研究（仅硫酸雌酮）中，雌二醇（胞质溶胶+0.6M KCl核提取物）的浓度为293±50pg/mg DNA，加入他莫昔芬后降至26±5pg/mg DNA，加入4-羟基他莫昔芬后降至9±2pg/mg DNA，加入N-去甲基他莫昔芬后降至24±7pg/mg DNA，加入顺式他莫昔芬后降至32±6pg/mg DNA。结论是，硫酸雌酮在该乳腺癌细胞系对雌激素的生物学反应中可能起重要作用，他莫昔芬及其衍生物会阻断硫酸雌酮向雌二醇的转化。雌二醇浓度的降低可能是由于雌激素受体系统的存在，但抗雌激素药物的其他作用方式仍有待探索。
