Antiestrogens estrogen receptor activation mechanisms

Fig. 6.2. Proposed mechanisms of action of pure antiestrogens (fulvestrant). 1 Fulvestrant (ICI) binds to estrogen receptor (ER). 2 Fulvestrant binding to ER accelerates receptor degradation ( ER down-regulator ). 3 Rate of dimerization and nuclear localization of fulvestrant-ER complex is reduced. 4 Reduced binding of fulvestrant-ER to ERE. 5 No transcription of estrogen-responsive genes since AF-1 and AF-2 are inactive, no coactivators are recruited and the activity of RNA polymerase II is not activated (or inhibited) (Wakeling 2000)...

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