Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells.
Arrestin domain-containing 3 (ARRDC3) is a tumor suppressor whose expression is either lost or suppressed in basal-like breast cancer (BLBC). However, the mechanism by which BLBC suppresses ARRDC3 expression is not established. Here, we show that expression of ARRDC3 in BLBC cells is suppressed at the transcriptional level. Suppression of ARRDC3 expression in BLBC cells involves epigenetic silencing as inhibitors of class III histone deacetylases (HDACs) significantly restores ARRDC3 levels in BLBC cells. SIRT2, among class III HDACs, plays a major role in epigenetic silencing of ARRDC3 in MDA-MB-231 cells. Acetylation levels of the ARRDC3 promoter in BLBC cells is significantly lower than that of other sub-types of BC cells. Chromatin immunopreciptitation analysis established SIRT2 binding at ARRDC3 promoter in BLBC cells. Our studies indicate that SIRT2 dependent epigenetic silencing of ARRDC3 is one of the important events that may contribute to the aggressive nature of BLBC cells.
Department of Physiology and Stephenson cancer center, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
Young Hwa
YH
Soung
Department of Molecular and Cellular Physiology Louisiana State University Health Science Center Shreveport, Louisiana 71130.
Kevin
K
Pruitt
Department of Physiology and Stephenson cancer center, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
Jun
J
Chung
D000107:Acetylation; D017209:Apoptosis / Q000187:drug effects; D019390:Arrestins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C508469:ARRDC3 protein, human; D019390:Arrestins; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D006655:Histone Deacetylases