ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression†
Kensuke Kumamoto
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorKaori Fujita
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorReiko Kurotani
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorMotonobu Saito
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorMotoko Unoki
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Laboratory for Biomarker, The Institute of Physical and Chemical Research, RIKEN, Tokyo, Japan
Search for more papers by this authorNobutoshi Hagiwara
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorHideaki Shiga
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorElise D. Bowman
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorNozomu Yanaihara
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorShu Okamura
Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan
Search for more papers by this authorMakoto Nagashima
Department of Surgery, Toho University Sakura Medical Center, Chiba, Japan
Search for more papers by this authorKotaro Miyamoto
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorSeiichi Takenoshita
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorJun Yokota
Biology Division, National Cancer Center Research Institute, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Curtis C. Harris
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Fax: +301-496-0497.
Laboratory of Human Carcinogenesis, CCR, NCI, NIH, 37 Convent Drive, Building 37, Room 3068, Bethesda, Maryland 20892-4258, USASearch for more papers by this authorKensuke Kumamoto
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorKaori Fujita
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorReiko Kurotani
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorMotonobu Saito
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorMotoko Unoki
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Laboratory for Biomarker, The Institute of Physical and Chemical Research, RIKEN, Tokyo, Japan
Search for more papers by this authorNobutoshi Hagiwara
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorHideaki Shiga
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorElise D. Bowman
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorNozomu Yanaihara
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Search for more papers by this authorShu Okamura
Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan
Search for more papers by this authorMakoto Nagashima
Department of Surgery, Toho University Sakura Medical Center, Chiba, Japan
Search for more papers by this authorKotaro Miyamoto
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorSeiichi Takenoshita
Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorJun Yokota
Biology Division, National Cancer Center Research Institute, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Curtis C. Harris
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Fax: +301-496-0497.
Laboratory of Human Carcinogenesis, CCR, NCI, NIH, 37 Convent Drive, Building 37, Room 3068, Bethesda, Maryland 20892-4258, USASearch for more papers by this authorThis article is a US Government work and, as such, is in the public domain in the United States of America.
Abstract
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. Published 2009 UICC.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
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| IJC_24437_sm_SuppFig1.tif378.4 KB | Supporting Information Figure 1. |
| IJC_24437_sm_SuppFig2.tif35 KB | Supporting Information Figure 2. |
| IJC_24437_sm_SuppFig3.tif46.9 KB | Supporting Information Figure 3. |
| IJC_24437_sm_SuppTable1.tif38.5 KB | Supporting Information Table 1. |
| IJC_24437_sm_SuppTable2.tif42.2 KB | Supporting Information Table 2. |
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