Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase
Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase
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DOI：
10.1158/0008-5472.can-05-0829
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发表时间：
2005-11-01
期刊：
影响因子：
11.2
通讯作者：
Huh, N
中科院分区：
文献类型：
--
作者：
Abarzua, F;Sakaguchi, M;Huh, N
在恶性转化和进展过程中发生的基因改变可能成为基因治疗的潜在靶点。我们先前发现REIC/DKK-3是一个在许多人类癌症中表达降低的基因。在这里，我们发现在人类前列腺癌组织中，REIC/DKK-3的表达以一种与分期相关的方式持续降低。强制表达REIC/DKK-3可诱导内源性REIC/DKK-3表达缺失的人前列腺癌细胞系的凋亡，但不能诱导表达REIC/DKK-3的正常前列腺上皮细胞和间质细胞的凋亡。细胞凋亡涉及c-jun-NH2-激酶的激活、Bax的线粒体易位和Bcl2的减少。单次注射携带REIC/DKK-3的腺病毒载体对人前列腺癌异种移植瘤有显著的抗肿瘤作用。因此，REIC/DKK-3基因可能成为前列腺癌基因治疗的新靶点。
Alteration in genes which takes place during malignant conversion and progression could be potential targets for gene therapy. We previously identified REIC/Dkk-3 as a gene whose expression is reduced in many human cancers. Here, we showed that expression of REIC/Dkk-3 was consistently reduced in human prostate cancer tissues in a stage-dependent manner. Forced expression of REIC/Dkk-3 induced apoptosis in human prostate cancer cell lines lacking endogenous REIC/Dkk-3 expression but not in REIC/Dkk3-proficient normal prostate epithelial and stromal cells. The apoptosis involved c-jun-NH2-kinase activation, mitochondrial translocation of Bax, and reduction of Bcl-2. A single injection of an adenovirus vector carrying REIC/Dkk-3 showed a dramatic antitumor effect on a xenotransplanted human prostate cancer. Thus, REIC/Dkk-3 could be a novel target for gene-based therapy of prostate cancer.