Calcium prevents tumorigenesis in a mouse model of colorectal cancer.
Calcium prevents tumorigenesis in a mouse model of colorectal cancer.
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钙可预防结直肠癌小鼠模型中的肿瘤发生
DOI：
10.1371/journal.pone.0022566
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fang JY
中科院分区：
文献类型：
--
作者：
Wang JL;Lin YW;Chen HM;Kong X;Xiong H;Shen N;Hong J;Fang JY
背景和目的钙作为结直肠癌（CRC）化学预防的介质已被提出，但其预防作用的综合机制尚不清楚。因此，我们开展了这项研究，以评估钙介导的预防1,2-二甲基肼（DMH）诱导的小鼠结直肠癌的可能作用和机制。方法采用4×44 K Agilent全基因组寡核苷酸芯片对DMH +钙组小鼠非肿瘤结直肠组织6个样本和DMH组与对照组各3个样本进行杂交，采用实时聚合酶链反应（real-time polymerase chain reaction， PCR）对所选基因进行验证。使用KEGG和基因本体（GO）分析对微阵列数据进行功能分析。利用Pathway Studio软件对枢纽基因进行鉴定。结果DMH组和DMH +钙组肿瘤发生率分别为90%和40%。基因芯片表达分析显示，与DMH组相比，DMH +钙组中S100a9、Defa20、Mmp10、Mmp7、Ptgs2和Ang2是下调最多的基因，而Per3、Tef、Rnf152和Prdx6则显著上调。功能分析显示，DMH +钙组Wnt、细胞周期和花生四烯酸通路显著下调，与细胞分化、细胞周期、增殖、细胞死亡、粘附和细胞迁移相关的GO项受到显著影响。叉头盒M1 （FoxM1）和核因子κ b （NF-κB）被认为是有效的枢纽基因。结论在dmh诱导的CRC小鼠模型中，复杂的基因表达改变涉及多种途径和GO术语的改变，其机制是全面的。然而，钙如何调节这些事件仍有待研究。
Background and Aim Calcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet clear. Hence, we conducted this study to evaluate the possible roles and mechanisms of calcium-mediated prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice. Methods For gene expression analysis, 6 non-tumor colorectal tissues of mice from the DMH + Calcium group and 3 samples each from the DMH and control groups were hybridized on a 4×44 K Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction (PCR). Functional analysis of the microarray data was performed using KEGG and Gene Ontology (GO) analyses. Hub genes were identified using Pathway Studio software. Results The tumor incidence rates in the DMH and DMH + Calcium groups were 90% and 40%, respectively. Microarray gene expression analysis showed that S100a9, Defa20, Mmp10, Mmp7, Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef, Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group compared with the DMH group. Functional analysis showed that the Wnt, cell cycle, and arachidonic acid pathways were significantly downregulated in the DMH + Calcium group, and that the GO terms related to cell differentiation, cell cycle, proliferation, cell death, adhesion, and cell migration were significantly affected. Forkhead box M1 (FoxM1) and nuclear factor kappa-B (NF-κB) were considered as potent hub genes. Conclusion In the DMH-induced CRC mouse model, comprehensive mechanisms were involved with complex gene expression alterations encompassing many altered pathways and GO terms. However, how calcium regulates these events remains to be studied.
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影响因子：
--
作者：
Bonnet A;Lagarrigue S;Liaubet L;Robert-Granié C;Sancristobal M;Tosser-Klopp G
通讯作者：
Tosser-Klopp G
DOI：
10.1158/1940-6207.capr-08-0157
发表时间：
2009-03
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Fedirko V;Bostick RM;Flanders WD;Long Q;Shaukat A;Rutherford RE;Daniel CR;Cohen V;Dash C
通讯作者：
Dash C
DOI：
10.1016/j.bbamcr.2007.10.015
发表时间：
2008-02-01
影响因子：
5.1
作者：
Ghavami, Saeld;Kerkhoff, Claus;Los, Marek
通讯作者：
Los, Marek
影响因子：
29
作者：
Gachon, Federic;Olela, Fabienne Fleury;Schibler, Ueli
通讯作者：
Schibler, Ueli
影响因子：
6.4
作者：
Ding, Eric L.;Mehta, Saurabh;Giovannucci, Edward L.
通讯作者：
Giovannucci, Edward L.