delta-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles.
delta-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles.
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DOI：
10.1186/1476-4598-8-19
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发表时间：
2009-03-10
期刊：
影响因子：
37.3
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Zeng Y;Abdallah A;Lu JP;Wang T;Chen YH;Terrian DM;Kim K;Lu Q
δ-Catenin是β-catenin/armadillo结构域超家族蛋白的独特成员，其主要表达局限于脑组织。然而，δ-连环蛋白在人前列腺癌中上调，尽管δ-连环蛋白过表达在前列腺癌中的作用尚不清楚。我们假设δ-连环蛋白通过改变细胞周期调控和细胞存活的基因谱在前列腺癌进展中起直接作用。我们采用基因转染和小干扰RNA来证明增加δ-连环蛋白表达促进前列腺癌细胞活力，而其敲低抑制前列腺癌细胞活力。δ-Catenin促进前列腺癌细胞在软琼脂中的集落形成以及裸鼠移植瘤的生长。缺失犰狳结构域外的氨基末端或羧基末端序列消除了δ-连环蛋白的促肿瘤作用。定量RT 2 Profiler™ PCR阵列证实了涉及细胞周期和存活调节的基因改变。δ-Catenin过表达上调细胞周期蛋白D1和cdc 34，增加磷酸化组蛋白H3，并促进有丝分裂的进入。此外，δ-catenin过表达导致细胞存活基因Bcl-2和survivin的表达增加，同时减少细胞周期抑制因子p21 Cip 1。总之，我们的研究表明，在人类前列腺癌中δ-连环蛋白表达增加的至少一个后果是细胞周期和存活基因谱的改变，从而促进肿瘤进展。
δ-Catenin is a unique member of β-catenin/armadillo domain superfamily proteins and its primary expression is restricted to the brain. However, δ-catenin is upregulated in human prostatic adenocarcinomas, although the effects of δ-catenin overexpression in prostate cancer are unclear. We hypothesized that δ-catenin plays a direct role in prostate cancer progression by altering gene profiles of cell cycle regulation and cell survival. We employed gene transfection and small interfering RNA to demonstrate that increased δ-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. δ-Catenin promoted prostate cancer cell colony formation in soft agar as well as tumor xenograft growth in nude mice. Deletion of either the amino-terminal or carboxyl-terminal sequences outside the armadillo domains abolished the tumor promoting effects of δ-catenin. Quantitative RT2 Profiler™ PCR Arrays demonstrated gene alterations involved in cell cycle and survival regulation. δ-Catenin overexpression upregulated cyclin D1 and cdc34, increased phosphorylated histone-H3, and promoted the entry of mitosis. In addition, δ-catenin overexpression resulted in increased expression of cell survival genes Bcl-2 and survivin while reducing the cell cycle inhibitor p21Cip1. Taken together, our studies suggest that at least one consequence of an increased expression of δ-catenin in human prostate cancer is the alteration of cell cycle and survival gene profiles, thereby promoting tumor progression.
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DOI：
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发表时间：
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