Identification of Pbx1, a potential oncogene, as a Notch3 target gene in ovarian cancer.
Identification of Pbx1, a potential oncogene, as a Notch3 target gene in ovarian cancer.
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DOI：
10.1158/0008-5472.can-08-0517
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发表时间：
2008-11-01
期刊：
影响因子：
11.2
通讯作者：
Wang TL
中科院分区：
文献类型：
--
作者：
Park JT;Shih IeM;Wang TL
最近在卵巢癌中发现了Notch 3基因扩增，但参与卵巢癌发展的Notch 3效应子仍然难以捉摸。在这项研究中，我们已经确定了Pbx 1，造血系统恶性肿瘤的原癌基因，作为Notch 3的靶基因。Pbx 1的表达受Notch 3激活的转录调控，Notch 3/CSL蛋白复合物直接结合到含有CSL结合序列的Pbx 1启动子片段。γ-分泌酶抑制剂的生长抑制作用可以部分逆转异位Pbx 1的表达。此外，通过Pbx 1 shRNA敲低的功能研究表明，Pbx 1是细胞增殖和致瘤性所必需的。综上所述，上述发现表明Pbx 1是一个直接受Notch 3调控的基因，介导了Notch 3在卵巢癌中的生存信号。
Notch3 gene amplification has recently been identified in ovarian cancer but the Notch3 effectors that are involved in the development of ovarian cancer remain elusive. In this study, we have identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a Notch3 target gene. Pbx1 expression is transcriptionally regulated by Notch3 activation, and Notch3/CSL protein complex directly binds to the Pbx1 promoter segment harboring the CSL binding sequence. The growth-inhibitory effect of gamma-secretase inhibitor could be partially reversed by ectopic Pbx1 expression. Furthermore, functional studies by Pbx1 shRNA knockdown demonstrate that Pbx1 is essential for cell proliferation and tumorigenicity. Taken together, the above findings indicate that Pbx1 is a direct Notch3-regulated gene that mediates the survival signal of Notch3 in ovarian cancer.