Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid.
Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid.
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DOI：
10.1158/0008-5472.919.65.3
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发表时间：
2005-02
期刊：
影响因子：
11.2
通讯作者：
C. Di;S. Liao;D. C. Adamson;T. Parrett;D. Broderick;Qun Shi;C. Lengauer;Jordan M. Cummins;V. V
中科院分区：
文献类型：
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作者：
C. Di;S. Liao;D. C. Adamson;T. Parrett;D. Broderick;Qun Shi;C. Lengauer;Jordan M. Cummins;V. V
通过永久性髓母细胞瘤细胞系的数字核型分析，我们发现同源盒基因OTX2在三个细胞系中扩增超过10倍。基因表达分析表明，OTX2转录本在14 15（93%）间变性组织病理学特征的髓母细胞瘤以高水平存在。敲低OTX2表达的siRNA抑制髓母细胞瘤细胞生长在体外，而药理剂量的全反式维甲酸抑制OTX2的表达和诱导细胞凋亡，仅在髓母细胞瘤细胞系表达OTX2。这些观察结果表明，OTX2是必不可少的间变性髓母细胞瘤的发病机制，这些肿瘤可能适合全反式维甲酸治疗。
Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid.