Methyl and bromo derivatives of estradiol are agonistic ligands for the estrogen receptor of MCF-7 breast cancer cells.
The binding affinity and relative estrogenic potency of 2-bromo-, 4-bromo-, 2-methyl- and 4-methylestradiol was evaluated in MCF-7 breast cancer cells. The relative binding affinities compared to estradiol were 47% for 2-methyl-, 25% for 4-methyl-, 37% for 4-bromo- and 17% for 2-bromoestradiol. However, both 2- and 4-methyl- as well as 2- and 4-bromoestradiol were able (a) to translocate the cytosolic estrogen receptor into the nucleus and (b) to induce the progesterone receptor in a concentration dependent manner. Finally, all ring-A substituted estrogens used in this study induced the pS2 mRNA as demonstrated by Northern-blotting. From these findings we conclude that 2-bromo-, 4-bromo-, 2-methyl- and 4-methylestradiol are agonistic ligands for the estrogen receptor in MCF-7 breast cancer cells.
Vollmer
G
G
Institut für Biochemische Endokrinologie, Medizinische Universität zu Lübeck, Fed. Rep. Germany.
Wünsche
W
W
Schütze
N
N
Feit
B
B
Knuppen
R
R
D015152:Blotting, Northern; D001943:Breast Neoplasms; D015536:Down-Regulation; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C037233:2-methylestradiol; D004958:Estradiol; C037234:4-methylestradiol