17 ALPHA-ESTRADIOL IS A BIOLOGICALLY-ACTIVE ESTROGEN IN HUMAN-BREAST CANCER-CELLS IN TISSUE-CULTURE
17 ALPHA-ESTRADIOL IS A BIOLOGICALLY-ACTIVE ESTROGEN IN HUMAN-BREAST CANCER-CELLS IN TISSUE-CULTURE
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DOI：
10.1210/endo-107-4-884
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发表时间：
1980-01-01
期刊：
影响因子：
4.8
通讯作者：
MCGUIRE, WL
中科院分区：
文献类型：
--
作者：
EDWARDS, DP;MCGUIRE, WL
The biological effects of 17.alpha.-estradiol (17.alpha.-E) and its interaction with estrogen receptors were studied in the MCF-7 human breast cancer cell line. Competition for [3H]17.beta.-estradiol ([3H]17.beta.-E) binding shows that 17.alpha.-E binds to receptor with high affinity and has a Kd estimated to be 0.7 nM. Upon binding with 17.alpha.-E, the cytosol receptor is translocated to the nucleus and is then rapidly depleted or processed in the same manner as the 17.beta.-E-receptor complex. The nuclear 17.alpha.-E-receptor complex was determined to be biologically active by its ability to stimulate an increase in the progesterone [PG] receptor content and to reverse antiestrogen inhibition of cellular proliferation and DNA polymerase activity. The estrogenic potency of 17.alpha.-E, estimated from the dose-response curves as the mean effective dose in stimulating PG receptor content and in reversing antiestrogen inhibition, is .apprx. 1/10 the potency of 17.beta.-E. Competition curves show that 17.alpha.-E binds to the cytosol estrogen receptor with 1/3 the affinity of 17.beta.-E, so the correlation between relative binding affinity and biological potency is not perfect. The correlation is reasonably good compared with that in animal studies, in which 17.alpha.-E displays negligible biological activity. Gas chromatography and mass spectrometry rule out the possibility that the observed estrogenic activity of 17.alpha.-E was due to contamination of the preparation with the more active 17.beta.-E. The enhanced estrogenic potency of 17.alpha.-E in MCF-7 cells raises the question of whether the stereospecificity and, thus, the sensitivity of the estrogen receptors in breast cancer cells may be different than those in normal target tissues. Enhanced estrogenic activity may also be due simply to the nature of the tissue culture system, which allows continuous exposure of the cells to hormone, a condition which may not be achieved in some animal studies.
