Activation of β-catenin signaling and its cross talk with estrogen and histone deacetylases in human uterine fibroids

Context: Uterine Fibroid (UF) is the most common benign tumor in myometrium (MM) of reproductive age women. However, mechanism underlying disease pathogenesis is largely unknown. Objective: To explore the link between nuclear β-catenin and UF phenotype and β-catenin cross-talk with estrogen and histone deacetylases (HDACs). Design protein/RNA levels of β-catenin (CTNNB1), its responsive markers [CyclinD1, c-Myc], Androgen receptor (AR), p27 and class-I HDACs were measured in matched UF/MM tissues or cell populations. Chemical inhibition/activation and genetic knockdown (KD) of CTNNB1 were performed and their effects on UF phenotype were measured. Anti-UF Effect of two HDAC inhibitors (HDACis) was evaluated. Main Outcome Measure: β-catenin nuclear translocation in response to β-catenin inhibition/activation, estrogen and HDACis in UF cells. Results: UF tissues/cells showed significantly higher expression of nuclear β-catenin, CyclinD1, C-Myc, and HDACs (1, 2, 3, 8) than MM. Estradiol ind...