Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation.
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.
Gazzerro
Patrizia
P
Dipartimento di Patologia generale, Seconda Università degli studi di Napoli, Via Luigi de Crecchio 7, I-80138 Naples, Italy.
Abbondanza
Ciro
C
D'Arcangelo
Andrea
A
Rossi
Mariangela
M
Medici
Nicola
N
Moncharmont
Bruno
B
Puca
Giovanni Alfredo
GA
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D016259:Genes, myc / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000494:pharmacology; D011960:Receptors, Estrogen; D016160:Retinoblastoma Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D004958:Estradiol; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human