Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis.

ABSTRACT: Osteosarcoma is a malignant tumor in the bone, which originates from normal osteoblasts or osteoblast precursors. Normal osteoblasts express estrogen receptor alpha (ERα); however, osteosarcomas do not express ERα due to promoter DNA methylation. Here we show that treatment of 143B osteosarcoma cells with decitabine (DAC, 5-Aza-2'-deoxycytidine) induces expression of ERα and leads to decreased proliferation and concurrent induction of osteoblast differentiation. DAC exposure reduced protein expression of metastasis-associated markers VIMENTIN, SLUG, ZEB1, and MMP9, with a concurrent decrease in mRNA expression of known stem cell markers SOX2, OCT4, and NANOG. Treatment with 17β-estradiol (E2) synergized with DAC to reduce proliferation. Overexpression of ERα inhibited proliferation and ind

SUBMITTER: Lillo Osuna MA 

PROVIDER: S-EPMC6420872 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature