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DAXX silencing suppresses mouse ovarian surface epithelial cell growth by inducing senescence and DNA damage

Wei-Wei Pan1, Fa-Ping Yi, Li-Xian Cao

  • 1Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing, China.

Gene
|April 2, 2013
PubMed

Insights

Deleting Daxx in mouse ovarian surface epithelium (mOSE) cells accelerated senescence and DNA damage, suggesting Daxx as a potential anti-cancer target for ovarian cancer.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Mouse ovarian surface epithelium (mOSE) cells are crucial for ovarian function and are implicated in ovarian cancer development.
  • Death-associated protein DAXX and promyelocytic leukemia protein nuclear bodies (PML-NBs) are involved in gene regulation and programmed cell death.
  • The specific role of DAXX in mOSE cells remains largely unexplored.

Purpose of the Study:

  • To investigate the function of DAXX in primary mouse ovarian surface epithelium (mOSE) cells.
  • To determine the impact of DAXX manipulation on mOSE cell behavior, including senescence and DNA damage.
  • To explore DAXX's potential as a therapeutic target in ovarian cancer.

Main Methods:

  • Overexpression and depletion of DAXX in primary mOSE cells.
  • Assessment of senescence markers and DNA damage.
  • Analysis of cell cycle progression.
  • Investigation of DAXX interactions with PML bodies.

Main Results:

  • Daxx deletion accelerated cellular senescence in a p53/p21-dependent pathway.
  • DAXX depletion promoted DNA damage through interaction with PML bodies.
  • Cell cycle progression was not significantly affected by Daxx manipulation.

Conclusions:

  • DAXX plays a critical role in maintaining mOSE cell homeostasis.
  • Loss of DAXX function may contribute to the transformation of mOSE cells towards an oncogenic phenotype.
  • DAXX represents a potential therapeutic target for ovarian cancer treatment.
Keywords:
CCAAT/enhancer-binding protein betaCEBPβDAXXDNADNA damageDTTEDTAEGFETS1FBSGFPITSInsulin–Transferrin–SeleniumOvarian surface epitheliumPAX5PBSPCRPIPMLPML-NBsPML-oncogenic domainsPODsSA-β -galSenescenceTUNELTdT-mediated dUTP Nick-End LabelingdNTPdeath-associated proteindeoxyribonucleic aciddeoxyribonucleotide triphosphatedithiothreitolepidermal growth factorethylenediamine tetraacetic acidfetal bovine serumgreen fluorescent proteinmOSEmouse ovarian surface epitheliumpaired box 5phosphate-buffered salinepolymerase chain reactionpromyelocytic leukemia proteinpromyelocytic leukemia protein nuclear bodiespropidium iodidesenescence-associated β-galactosidasev-ets erythroblastosis virus E26 oncogene homolog 1 (avian)

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