ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression.
ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression.
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DOI：
10.1002/ijc.24437
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发表时间：
2009-09-15
影响因子：
6.4
通讯作者：
Harris CC
中科院分区：
文献类型：
--
作者：
Kumamoto K;Fujita K;Kurotani R;Saito M;Unoki M;Hagiwara N;Shiga H;Bowman ED;Yanaihara N;Okamura S;Nagashima M;Miyamoto K;Takenoshita S;Yokota J;Harris CC
生长抑制因子2（ING 2）通过与甲基化组蛋白H3 K4残基结合并将HDAC复合物募集到该区域，与染色质重塑和基因表达调控相关。本研究的目的是探讨ING 2在结肠癌中的表达调控及表达上调的临床意义。在这里，我们发现，在我们检查的45%的结直肠癌病例中，结肠癌组织中的ING 2 mRNA水平比正常粘膜中的ING 2 mRNA水平增加两倍以上。在ING 2启动子区发现一个推测的NF-κB结合位点。我们通过EMSA和荧光素酶分析证实NF-κB可以与ING 2启动子结合。随后的微阵列分析显示，ING 2上调基质金属蛋白酶13（MMP 13）的表达，这增强了癌症的侵袭和转移。在ING 2过表达和敲低实验中均证实了ING 2对MMP 13表达的调节。通过ING 2与HDAC 1或与mSin 3A的共表达进一步诱导MMP 13表达，表明ING 2-HDAC 1-mSin 3A复合物成员调节MMP 13的表达。进行体外侵袭测定以确定ING 2上调的功能意义。ING 2过表达的细胞表现出更大的侵袭潜力。总之，ING 2的上调与结肠癌和MMP 13依赖的细胞侵袭相关，表明ING 2表达可能与癌症侵袭和转移有关。
Inhibitor of growth 2 (ING2) is associated with chromatin remodeling and regulation of gene expression by binding to a methylated histone H3K4 residue and recruiting HDAC complexes to the region. The aim of our study is to investigate the regulation of ING2 expression and the clinical significance of upregulated ING2 in colon cancer. Here, we show that the ING2 mRNA level in colon cancer tissue increased to more than twice than that in normal mucosa in the 45% of colorectal cancer cases that we examined. A putative NF-κB binding site was found in the ING2 promoter region. We confirmed that NF-κB could bind to the ING2 promoter by EMSA and luciferase assays. Subsequent microarray analyses revealed that ING2 upregulates expression of matrix metalloproteinase 13 (MMP13), which enhances cancer invasion and metastasis. ING2 regulation of MMP13 expression was confirmed in both ING2 overexpression and knock down experiments. MMP13 expression was further induced by coexpression of ING2 with HDAC1 or with mSin3A, suggesting that the ING2-HDAC1-mSin3A complex members regulates expression of MMP13. In vitro invasion assay was performed to determine functional significance of ING2 upregulation. ING2 overexpressed cells exhibited greater invasive potential. Taken together, upregulation of ING2 was associated with colon cancer and MMP13-dependent cellular invasion, indicating that ING2 expression might be involved with cancer invasion and metastasis.
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影响因子：
6.4
作者：
Ala-Aho, R;Johansson, N;Kähäri, VM
通讯作者：
Kähäri, VM
影响因子：
4.1
作者：
Clarke, JH;Letcher, AJ;Divecha, N
通讯作者：
Divecha, N
影响因子：
6.4
作者：
Hilska, Marja;Roberts, Peter J.;Laato, Matti
通讯作者：
Laato, Matti
影响因子：
4.6
作者：
Golubovskaya, Vita M.;Finch, Richard;Cance, William G.
通讯作者：
Cance, William G.
DOI：
10.1016/j.bbaexp.2004.03.002
发表时间：
2004-05-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Golubovskaya, V;Kaur, A;Cance, W
通讯作者：
Cance, W