Overexpression of cohesion establishment factor DSCC1 through E2F in colorectal cancer.
Overexpression of cohesion establishment factor DSCC1 through E2F in colorectal cancer.
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DOI：
10.1371/journal.pone.0085750
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Furukawa Y
中科院分区：
文献类型：
--
作者：
Yamaguchi K;Yamaguchi R;Takahashi N;Ikenoue T;Fujii T;Shinozaki M;Tsurita G;Hata K;Niida A;Imoto S;Miyano S;Nakamura Y;Furukawa Y
Ctf 18-复制因子C复合物包括Dscc 1（DNA复制和姐妹染色单体凝聚1），涉及姐妹染色单体凝聚，DNA复制和基因组稳定性在S。酿酒酵母和C.优美的我们先前在原发性结直肠癌细胞中进行了基因表达谱分析，以确定治疗结直肠癌的新分子靶点。从这项研究中揭示的癌症相关转录特征的一个特征是原癌基因DSCC 1的表达升高。在这里，我们询问了人类DSCC 1在结直肠癌中异常表达的分子基础及其促进癌细胞存活的能力。定量PCR和免疫组化分析证实，DSCC 1的表达水平在60-70%的结直肠肿瘤中与其匹配的非癌结肠粘膜相比升高。一致的DNA转录调控元件的推定DSCC 1启动子区域的计算机评估揭示了DNA结合蛋白的E2 F家族在控制DSCC 1表达中的潜在作用。RNAi介导的E2 F1的减少降低了结直肠癌细胞中DSCC 1的表达。获得和丧失功能的实验表明，DSCC 1参与癌细胞对遗传毒性刺激的反应。我们发现，E2 F依赖的DSCC 1表达赋予结直肠癌细胞的抗凋亡特性，其抑制可能是治疗结直肠癌的一个有用的选择。
Ctf18-replication factor C complex including Dscc1 (DNA replication and sister chromatid cohesion 1) is implicated in sister chromatid cohesion, DNA replication, and genome stability in S. cerevisiae and C. elegans. We previously performed gene expression profiling in primary colorectal cancer cells in order to identify novel molecular targets for the treatment of colorectal cancer. A feature of the cancer-associated transcriptional signature revealed from this effort is the elevated expression of the proto-oncogene DSCC1. Here, we have interrogated the molecular basis for deviant expression of human DSCC1 in colorectal cancer and its ability to promote survival of cancer cells. Quantitative PCR and immunohistochemical analyses corroborated that the expression level of DSCC1 is elevated in 60–70% of colorectal tumors compared to their matched noncancerous colonic mucosa. An in silico evaluation of the presumptive DSCC1 promoter region for consensus DNA transcriptional regulatory elements revealed a potential role for the E2F family of DNA-binding proteins in controlling DSCC1 expression. RNAi-mediated reduction of E2F1 reduced expression of DSCC1 in colorectal cancer cells. Gain- and loss-of-function experiments demonstrated that DSCC1 is involved in the viability of cancer cells in response to genotoxic stimuli. We reveal that E2F-dependent expression of DSCC1 confers anti-apoptotic properties in colorectal cancer cells, and that its suppression may be a useful option for the treatment of colorectal cancer.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Bieda, M;Xu, XQ;Farnham, PJ
通讯作者：
Farnham, PJ
影响因子：
8
作者：
Lin, YM;Furukawa, Y;Nakamura, Y
通讯作者：
Nakamura, Y
DOI：
10.1073/pnas.1434308100
发表时间：
2003-09-02
影响因子：
11.1
作者：
Bermudez, VP;Maniwa, Y;Hurwitz, J
通讯作者：
Hurwitz, J
影响因子：
30.8
作者：
Bennett, CB;Lewis, LK;Resnick, MA
通讯作者：
Resnick, MA