Hyper-expression of PAX2 in human metastatic prostate tumors and its role as a cancer promoter in an in vitro invasion model
Hyper-expression of PAX2 in human metastatic prostate tumors and its role as a cancer promoter in an in vitro invasion model
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DOI：
10.1002/pros.22687
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发表时间：
2013-09-01
期刊：
影响因子：
2.8
通讯作者：
Miki, Tsuneharu
中科院分区：
文献类型：
--
作者：
Ueda, Takashi;Ito, Saya;Miki, Tsuneharu
背景转移是许多生物学事件的结果，在此期间癌症干细胞转变为恶性状态。在这些事件中，前列腺癌细胞侵入宿主组织可以通过体外侵入模型来评估，并且被认为与膜蛋白的表达改变相关联。已知在胚胎发生期间调节器官发生的因子的失调功能促进许多类型的癌症的转移。PAX 2（配对盒2）是PAX转录因子家族的成员，可调节哺乳动物前列腺器官发生中的前列腺导管生长和分支。然而，PAX 2在前列腺癌发展中的作用仍有待确定。应用定量RT-PCR和免疫组化方法检测PAX 2在前列腺癌和正常前列腺上皮中的表达。使用用对照或PAX 2 siRNA转染的前列腺癌细胞系进行基质胶侵袭测定和基因阵列分析。在人类前列腺癌中，PAX 2在转移性癌症中高表达，但在非转移性癌症中表达水平较低。与此一致，PAX 2敲低在基质胶侵袭测定中抑制细胞生长和侵袭。基因本体分析显示PAX 2基因敲除后，许多细胞膜蛋白表达下调。我们的数据表明，PAX 2高表达促进前列腺癌细胞中转移状态的发展，推测是通过上调细胞膜蛋白的表达。(c)2013 Wiley Periodicals，Inc.
BACKGROUND. Metastasis is a consequence of many biological events, during which cancer stem cells are shifted into a malignant state. Among these events, invasion of prostate cancer cells into host tissues is possible to be assessed by means of an in vitro invasion model, and is thought to be coupled to altered expression of membrane proteins. Dysregulated functions of the factors regulating organogenesis during embryogenesis are known to facilitate metastasis of many types of cancers. PAX2 (paired box 2) is a member of the PAX transcription factor family, which regulates prostatic ductal growth and branching in organogenesis of mammalian prostates. However, the role of PAX2 in prostate cancer development remains to be determined.METHODS. PAX2 expression in human prostate cancers and normal prostate epithelium were examined by quantitative RT-PCR and immunohistochemistry. Matrigel invasion assay and a gene array analysis were performed using prostate cancer cell lines transfected with either control or PAX2 siRNA.RESULTS. In human prostate cancers, PAX2 was hyper-expressed in metastatic cancers, but was expressed at lower levels in non-metastatic cancers. Consistent with this, PAX2 knockdown repressed cell growth and invasion in a Matrigel invasion assay. Gene ontology analysis revealed that many cell membrane proteins were downregulated after PAX2 knockdown.CONCLUSIONS. Our data suggested that PAX2 hyper-expression promotes the development of the metastatic state in prostate cancer cells, presumably through upregulating the expression of cell membrane proteins. (c) 2013 Wiley Periodicals, Inc.