Abnormal Properties of Mutants in the Hinge Region of ERα: Implications in Breast Cancer

摘要: In the search for differences between estrogen receptor (ER) α and ERβ, we proved that ERα but not ERβ directly interacts with calmodulin (CaM) through hinge region. The transcriptional activity of a mutant unable to interact CaM becomes insensitive inhibition by antagonists (W7). These residues are acetylated p300 substitution lysine 302 303 other enhance ERα-hormone sensitivity, suggesting acetylation normally suppresses ligand sensitivity. Also, somatic mutation K303R has been identified in early premalignant breast lesions. binds E shows increased E-induced activation proliferation response when transfected into cancer cell (BC) lines. Herein, show mutations K303A, render an therefore W7. K303 homodimers mutant/wt heterodimers sensitivity E. Contrary wt ERα, AP1 is inhibited estradiol (E2) OH-Tamoxifen (OH-TAM) both K303A mutants.