ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature.

ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature.
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ARID3B增加了卵巢肿瘤负担,并与癌细胞基因的特征有关。

DOI:
10.18632/oncotarget.2247
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发表时间:
2014-09-30
期刊:
影响因子:
--
通讯作者:
Cowden Dahl KD
Cowden Dahl KD
中科院分区:
其他
文献类型:
--
作者:
Roy L;Samyesudhas SJ;Carrasco M;Li J;Joseph S;Dahl R;Cowden Dahl KD

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卵巢癌是最致命的妇科恶性肿瘤,因为大多数患者在确诊时都有转移性疾病。因此,识别导致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,我们报道了DNA结合蛋白ARID3B在人卵巢肿瘤中过表达。为了确定ARID3B在体内是否具有致癌功能,将稳定表达ARID3B的卵巢癌细胞系注射到裸鼠体内。ARID3B过表达增加了肿瘤负担,降低了生存期。为了评估ARID3B如何在体内促进肿瘤生长,我们在肿瘤腹水细胞中鉴定了ARID3B诱导的基因。ARID3B诱导转移和肿瘤干细胞相关基因(CD44、LGR5、PROM1(CD133)和Notch2)的表达。此外,与对照细胞相比,ARID3B增加了CD133+(一种癌症干细胞标记物)细胞的数量。ARID3B表达导致CD133+细胞增多的同时伴随着紫杉醇耐药性的增强。我们的数据表明,ARID3B促进了CD133+细胞的产生,并在体内加速了卵巢癌的进展。
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 of CD133+ cells and increases ovarian cancer progression in vivo.
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