Overexpression of ERβ inhibits the proliferation through regulating TNG-β signaling pathway in osteosarcoma

Pathol Res Pract. 2019 Oct;215(10):152568. doi: 10.1016/j.prp.2019.152568. Epub 2019 Jul 27.

Abstract

The present study aimed to explore the potential anti-tumor effect of ERβ overexpression and investigate its related mechanism in osteosarcoma. Cell cycle and apoptosis rates were measured by flow cytometry. Cell proliferation and formation of autophagosome were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and dansylcadaverine (MDC) staining assay. Cell migration and invasion were detected by wound healing assay and transwell assay. Western blot analysis was designed to detect the protein expressions of surviving, Bax, LC-3 П, Beclin-1, ERβ, TβRⅠ, TβRⅡ, Smad2, Smad3 and Smad7. Real-Time fluorogenic PCR was designed to examine the mRNA expressions of surviving, Bax, ERβ, TβRⅠ, TβRII, Smad2, Smad3 and Smad7. The results showed that ERβ overexpression inhibited cell proliferation, migration and invasion, blocked cell cycle, and induced apoptosis and autophagy. Additionally, ERβ overexpression significantly inhibited the expression of surviving, TβRⅠ, TβRⅡ, Smad2 and Smad3. Meanwhile, the expressions of Bax, LC-3 П, Beclin-1 and Smad7 were dramatically upregulated by ERβ overexpression. In conclusion, ERβ overexpression could inhibit cell proliferation, migration and invasion, block cell cycle, and promote apoptosis and autophagy in OS by downregulating TNG-β signaling pathway.

Keywords: ERβ overexpression; Proliferation; TNG-; osteosarcoma; β signaling pathway.

MeSH terms

  • Apoptosis / genetics
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism*
  • Humans
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Signal Transduction / genetics*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • Estrogen Receptor beta
  • Transforming Growth Factor beta