title: DAXX silencing suppresses mouse ovarian surface epithelial cell growth by inducing senescence and DNA damage.
abstract: Mouse ovarian surface epithelium (OSE) is a single layer of cubodial epithelial cells that covers the ovary surface and is involved in regulating the secretion and transport of 17β-hydroxysteroid dehydrogenase. Recently, OSE cells have attracted particular interest as a major source of ovarian cancer. Death-associated protein DAXX along with PML (promyelocytic leukemia protein) nuclear bodies (PML-NBs) reportedly play roles in transcriptional regulation and apoptosis. However, little is known regarding a role for DAXX in mOSE cells. In this study, we both over-expressed DAXX and depleted DAXX in primary mOSE cells. We found that Daxx deletion accelerated senescence in a p53/p21-dependent manner and promoted DNA damage by interacting with PML bodies without affecting cell cycle progression. These results suggest that DAXX may transform mOSE cells to an ovarian oncogenic phenotype and may be an anti-cancer target.
authors.affiliation: Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Pan
authors.forename: Fa-Ping
authors.initials: FP
authors.lastname: Yi
authors.forename: Li-Xian
authors.initials: LX
authors.lastname: Cao
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Liu
authors.forename: Zhong-Fei
authors.initials: ZF
authors.lastname: Shen
authors.forename: You-Quan
authors.initials: YQ
authors.lastname: Bu
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Fan
authors.forename: Fang-Zhou
authors.initials: FZ
authors.lastname: Song
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D056970:Co-Repressor Proteins; D004249:DNA Damage; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D015689:Oncogene Protein p21(ras)
keywords: CCAAT/enhancer-binding protein beta; CEBPβ; DAXX; DNA; DNA damage; DTT; EDTA; EGF; ETS1; FBS; GFP; ITS; Insulin–Transferrin–Selenium; Ovarian surface epithelium; PAX5; PBS; PCR; PI; PML; PML-NBs; PML-oncogenic domains; PODs; SA-β -gal; Senescence; TUNEL; TdT-mediated dUTP Nick-End Labeling; dNTP; death-associated protein; deoxyribonucleic acid; deoxyribonucleotide triphosphate; dithiothreitol; epidermal growth factor; ethylenediamine tetraacetic acid; fetal bovine serum; green fluorescent protein; mOSE; mouse ovarian surface epithelium; paired box 5; phosphate-buffered saline; polymerase chain reaction; promyelocytic leukemia protein; promyelocytic leukemia protein nuclear bodies; propidium iodide; senescence-associated β-galactosidase; v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)