ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature
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Lynn Roy1, Serene J. Samyesudhas1, Martin Carrasco1, Jun Li2, Stancy Joseph1, Richard Dahl3 and Karen D. Cowden Dahl1,4,5
1 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana
2 Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, Indiana
3 Department of Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana
4 Department of Chemistry and Biochemistry and Eck Institute for Global Health, Notre Dame University, Notre Dame, Indiana
5 Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana
Karen D. Cowden Dahl , email:
Keywords: Ovarian cancer, transcription factor, cancer stem cells, metastasis, xenografts
Received: June 12, 2014 Accepted: July 22, 2014 Published: July 23, 2014
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.
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