Effects of the antiestrogens tamoxifen and raloxifene on the estrogen receptor transactivation machinery.
The influence of 17beta-estradiol (E2), tamoxifen (TAM) and raloxifen (RLX) on the proliferation of breast (BC) and endometrial carcinoma cell lines (EC) and the expression of different compounds of the estrogen receptor (ER)-transactivation machinery were studied. E2 stimulated the proliferation of BC, but had no effect on the EC. TAM showed a biphasic effect on ER-positive cell lines. RLX showed an antagonistic suppression or no effect. The expression of ERalpha was down-regulated by E2, but not affected by selective estrogen receptor modulators. ERbeta and progesterone receptor expressions were up-regulated by E2, TAM and OHT. This supports the hypothesis that ERbeta expression is also regulated via the ERalpha-pathway. The steroid receptor coactivator (SRC) AIB1 expression was slightly decreased by E2 but not by antiestrogens (antiE). TIF2 expression was increased by E2, TAM and RLX, but SRC-1 expression was not. In comparison, the expressions of ERbeta and progesterone receptor were strongly influenced by antiE, while the expression of SRCs was only slightly affected.
Glaeser
Michael
M
Department of Gynecology and Obstetrics, Heinrich-Heine-University, Duesseldorf, Germany.
Niederacher
Dieter
D
Djahansouzi
Sirus
S
Hanstein
Bettina
B
Dittrich
Ralf
R
Beckmann
Matthias W
MW
Fasching
Peter A
PA
Ackermann
Sven
S
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D004958:Estradiol