Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation

Exp Cell Res. 2006 Feb 1;312(3):340-9. doi: 10.1016/j.yexcr.2005.11.002. Epub 2005 Dec 13.


The retinoblastoma protein-interacting zinc-finger (RIZ) gene, a member of the nuclear protein methyltransferase superfamily, is characterized by the presence of the N-terminal PR domain. The RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the PR (PRDI-BF1 and RIZ homologous) domain, RIZ2 lacks it. RIZ gene expression is altered in a variety of human cancers and RIZ1 is now considered to be a candidate tumor suppressor. Estradiol treatment of MCF-7 cells produced a selective decrease of RIZ1 transcript and an increase of total RIZ mRNA. Experiments of chromatin immunoprecipitation indicated that RIZ2 protein expression was controlled by estrogen receptor and RIZ1 had a direct repressor function on c-myc gene expression. To investigate the role of RIZ gene products as regulators of the proliferation/differentiation transition, we analyzed the effects of forced suppression of RIZ1 induced in MCF-7 cells by siRNA of the PR domain-containing form. Silencing of RIZ1 expression stimulated cell proliferation, similar to the effect of estradiol on these cells, associated with a transient increase of c-myc expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Proliferation*
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Estradiol / pharmacology*
  • Female
  • Gene Expression*
  • Gene Silencing
  • Genes, myc / physiology
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • RNA, Messenger
  • RNA, Small Interfering / pharmacology
  • Receptors, Estrogen
  • Retinoblastoma Protein / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Estrogen
  • Retinoblastoma Protein
  • Transcription Factors
  • Estradiol
  • Histone-Lysine N-Methyltransferase
  • PRDM2 protein, human