title: ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature.
abstract: Ovarian cancer is the most deadly gynecological malignancy since most patients have metastatic disease at the time of diagnosis. Therefore, identification of critical pathways that contribute to ovarian cancer progression is necessary to yield novel therapeutic targets. Recently we reported that the DNA binding protein ARID3B is overexpressed in human ovarian tumors. To determine if ARID3B has oncogenic functions in vivo, ovarian cancer cell lines stably expressing ARID3B were injected intraperitoneally into nude mice. Overexpression of ARID3B increased tumor burden and decreased survival. To assess how ARID3B contributes to the increased tumor growth in vivo, we identified ARID3B induced genes in tumor ascites cells. ARID3B induced expression of genes associated with metastasis and cancer stem cells (CD44, LGR5, PROM1 (CD133), and Notch2). Moreover, ARID3B increased the number of CD133+ (a cancer stem cell marker) cells compared to control cells. The increase in CD133+ cells resulting from ARID3B expression was accompanied by enhanced paclitaxel resistance. Our data demonstrate that ARID3B boosts production CD133+ cells and increases ovarian cancer progression in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana.
authors.forename: Lynn
authors.initials: L
authors.lastname: Roy
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana.
authors.forename: Serene J
authors.initials: SJ
authors.lastname: Samyesudhas
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana.
authors.forename: Martin
authors.initials: M
authors.lastname: Carrasco
authors.affiliation: Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana.
authors.forename: Stancy
authors.initials: S
authors.lastname: Joseph
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana.
authors.forename: Richard
authors.initials: R
authors.lastname: Dahl
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana. Department of Chemistry and Biochemistry and Eck Institute for Global Health, Notre Dame University, Notre Dame, Indiana. Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Cowden Dahl
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; C120893:ARID3B protein, human; D015703:Antigens, CD; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D017239:Paclitaxel