Volume 1, Issue 3, Pages (April 2002)

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Volume 1, Issue 3, Pages 215-217 (April 2002) The secrets of selective estrogen receptor modulation: Cell-specific coregulation V.Craig Jordan Cancer Cell Volume 1, Issue 3, Pages 215-217 (April 2002) DOI: 10.1016/S1535-6108(02)00050-8

Figure 1 Integrated mechanism for the target site specific action of SERMs in breast or uterine cancer The two extremes of antiestrogenic or full estrogenic actions are shown. Estrogen-like actions could occur in cells expressing an excess of coactivators (CoAs) and/or a decrease in corepressors (CoRs). The charged surface of a tamoxifen ER complex at AF2b prevents CoR binding. The estrogenic action would be amplified by surface signaling with dimers of epidermal growth factor receptor (EGFR) and HER2/neu activating tyrosine kinases (tks). The phosphorylation cascade can activate AF-1 on ERα directly or activate the excess of CoAs in a high ER environment. Reduced levels of ER prevent the signal transduction pathway and promote antiestrogenic actions in a surface silent cell. Cancer Cell 2002 1, 215-217DOI: (10.1016/S1535-6108(02)00050-8)