INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling.
INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling.
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DOI：
10.1186/1475-2867-9-28
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发表时间：
2009-11-11
影响因子：
5.8
通讯作者：
Wieland I
中科院分区：
文献类型：
--
作者：
Filleur S;Hirsch J;Wille A;Schön M;Sell C;Shearer MH;Nelius T;Wieland I
编码整合复合物亚基 6 (INTS6) 的基因，以前被称为癌细胞 1 (DICE1，OMIM 604331) 中的缺失，被发现经常受到前列腺癌样本和细胞系中等位基因缺失和启动子高甲基化的影响。在前列腺癌细胞系 LNCaP 中检测到错义突变。总之，这些结果表明 INTS6/DICE1 是前列腺癌中假定的肿瘤抑制基因。在这项研究中，我们检测了 INTS6/DICE1 对前列腺癌细胞的生长抑制作用。与源自正常前列腺组织的细胞系 NPTX1532 相比，在前列腺癌细胞系 LNCaP、DU145 和 PC3 以及 CPTX1532 中检测到 INTS6/DICE1 mRNA 水平显着降低。在不依赖雄激素的 PC3 和 DU145 细胞系中，INTS6/DICE1 cDNA 的外源再表达显着抑制了它们在体外形成集落的能力。这种生长抑制并不是由于立即诱导细胞凋亡。相反，前列腺癌细胞停滞在细胞周期的 G1 期。 Wnt 信号通路成员的表达谱显示多个基因上调，包括蓬乱抑制剂 CXXC Finger 4 (CXXC4)、卷曲同源物 7 (FZD7)、转录因子 7-like 1 (TCF7L1) 和细胞周期蛋白 D1 下调。这些结果首次表明 INTS6/DICE1 功能、细胞周期调节和涉及 Wnt 信号通路成员的细胞间通讯之间的联系。
The gene encoding integrator complex subunit 6 (INTS6), previously known as deleted in cancer cells 1 (DICE1, OMIM 604331) was found to be frequently affected by allelic deletion and promoter hypermethylation in prostate cancer specimens and cell lines. A missense mutation has been detected in prostate cancer cell line LNCaP. Together, these results suggest INTS6/DICE1 as a putative tumor suppressor gene in prostate cancer. In this study, we examined the growth inhibitory effects of INTS6/DICE1 on prostate cancer cells. Markedly decreased INTS6/DICE1 mRNA levels were detected in prostate cancer cell lines LNCaP, DU145 and PC3 as well as CPTX1532 as compared to a cell line derived from normal prostate tissue, NPTX1532. Exogenous re-expression of INTS6/DICE1 cDNA in androgen-independent PC3 and DU145 cell lines substantially suppressed their ability to form colonies in vitro. This growth inhibition was not due to immediate induction of apoptosis. Rather, prostate cancer cells arrested in G1 phase of the cell cycle. Expression profiling of members of the Wnt signaling pathway revealed up-regulation of several genes including disheveled inhibitor CXXC finger 4 (CXXC4), frizzled homologue 7 (FZD7), transcription factor 7-like 1 (TCF7L1), and down-regulation of cyclin D1. These results show for the first time a link between INTS6/DICE1 function, cell cycle regulation and cell-cell communication involving members of the Wnt signaling pathway.
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影响因子：
5.3
作者：
OConnor, R;KauffmannZeh, A;Blattler, WA
通讯作者：
Blattler, WA
影响因子：
8
作者：
Wieland, I;Arden, KC;Weidle, UH
通讯作者：
Weidle, UH
DOI：
10.1073/pnas.90.18.8392
发表时间：
1993-09-15
影响因子：
11.1
作者：
PEAR, WS;NOLAN, GP;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
8
作者：
Röpke, A;Buhtz, P;Wieacker, PF
通讯作者：
Wieacker, PF
影响因子：
3.1
作者：
Wieland, I;Röpke, A;Wieacker, PF
通讯作者：
Wieacker, PF