Roy Lynn, Samyesudhas Serene J, Carrasco Martin, Li Jun, Joseph Stancy, Dahl Richard, Cowden Dahl Karen D
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana.
Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, Indiana.
Oncotarget. 2014 Sep 30;5(18):8355-66. doi: 10.18632/oncotarget.2247.
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.
卵巢癌是最致命的妇科恶性肿瘤，因为大多数患者在诊断时已患有转移性疾病。因此，确定促成卵巢癌进展的关键途径对于产生新的治疗靶点是必要的。最近我们报道DNA结合蛋白ARID3B在人类卵巢肿瘤中过表达。为了确定ARID3B在体内是否具有致癌功能，将稳定表达ARID3B的卵巢癌细胞系腹腔注射到裸鼠体内。ARID3B的过表达增加了肿瘤负荷并降低了生存率。为了评估ARID3B如何在体内促进肿瘤生长增加，我们在肿瘤腹水细胞中鉴定了ARID3B诱导的基因。ARID3B诱导了与转移和癌症干细胞相关的基因（CD44、LGR5、PROM1（CD133）和Notch2）的表达。此外，与对照细胞相比，ARID3B增加了CD133+（一种癌症干细胞标志物）细胞的数量。ARID3B表达导致的CD133+细胞增加伴随着紫杉醇耐药性的增强。我们的数据表明，ARID3B促进CD133+细胞的产生并增加体内卵巢癌的进展。
