RIZ1 is regulated by estrogen and suppresses tumor progression in endometrial cancer

Biochem Biophys Res Commun. 2017 Jul 22;489(2):96-102. doi: 10.1016/j.bbrc.2017.05.095. Epub 2017 May 18.

Abstract

Endometrial cancer (EC) is the estrogen-dependent gynecologic malignancy, however the molecular mechanism involved in the development and progression of EC remain unclear. The aim of this study was to investigate the role of RIZ1 in EC. Immunohistochemical analysis revealed that RIZ1was decreased in EC than in normal endometrium. Lower RIZ1 level was correlated with high-grade carcinoma (p = 0.048) and positive expression of ERα (p = 0.004). In EC cells, estrogen could down regulated the expression of RIZ1, however, ICI182,780 could up regulated the expression of RIZ1. Besides, in vitro and in vivo, RIZ1 could remarkably suppress tumor proliferation, metastasis and invasion. Our data support that RIZ1 was a novel tumor suppressor and could provide a potential therapeutic target in human EC.

Keywords: Endometrial carcinoma(EC); Estrogen receptor α (ERα); RIZ1; Tumor suppressor gene.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease Progression*
  • Down-Regulation*
  • Drug Screening Assays, Antitumor
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology*
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogens / metabolism*
  • Female
  • Fulvestrant
  • Histone-Lysine N-Methyltransferase / biosynthesis
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Structure-Activity Relationship
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • Estrogens
  • Nuclear Proteins
  • Transcription Factors
  • Fulvestrant
  • Estradiol
  • Histone-Lysine N-Methyltransferase
  • PRDM2 protein, human