Increased SPHK2 Transcription of Human Colon Cancer Cells in Serum‐Depleted Culture: The Involvement of CREB Transcription Factor
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- Naoki Mizutani
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
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- Yukari Omori
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
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- Koji Tanaka
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
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- Hiromi Ito
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
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- Akira Takagi
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
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- Tetsuhito Kojima
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
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- Masahiro Nakatochi
- Bioinformatics Section Center for Advanced Medicine and Clinical Research, Nagoya University Hospital Nagoya Japan
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- Hideo Ogiso
- Department of Hematology Kanazawa Medical University Kanazawa Japan
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- Yoshiyuki Kawamoto
- College of Life and Health Sciences Chubu University Kasugai Japan
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- Mitsuhiro Nakamura
- Department of Drug Information Gifu Pharmaceutical University Gifu Japan
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- Motoshi Suzuki
- Division of Molecular Carcinogenesis Nagoya University Graduate School of Medicine Nagoya Japan
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- Mamoru Kyogashima
- Department of Microbiology and Molecular Biology Nihon Pharmaceutical University Saitama Japan
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- Keiko Tamiya‐Koizumi
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
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- Yoshinori Nozawa
- Tokai Gakuin University Kakamigahara Japan
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- Takashi Murate
- Department of Pathophysiological Laboratory Science Nagoya University Graduate School of Medicine Nagoya Japan
書誌事項
- 公開日
- 2015-08-14
- 資源種別
- journal article
- 権利情報
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1002/jcb.25173
- 公開者
- Wiley
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説明
<jats:title>ABSTRACT</jats:title><jats:sec><jats:label /><jats:p>Sphingosine kinases (SPHK) are important to determine cells' fate by producing sphingosine 1‐phosphate. Reportedly, exogenous SPHK2 overexpression induces cell cycle arrest or cell death. However, the regulatory mechanism of SPHK2 expression has not been fully elucidated. Here, we analyzed this issue using human colon cancer cell lines under various stress conditions. Serum depletion (FCS(‐)) but not hypoxia and glucose depletion increased mRNA, protein and enzyme activity of SPHK2 but not SPHK1. In HCT116 cells mostly used, SPHK2 activity was predominant over SPHK1, and serum depletion increased both nuclear and cytoplasmic SPHK2 activity. Based on previous reports analyzing cellular response after serum depletion, the temporal changes of intracellular signaling molecules and candidate transcription factors for SPHK2 were examined using serum‐depleted HCT116 cells, and performed transfection experiments with siRNA or cDNA of candidate transcription factors. Results showed that the rapid and transient JNK activation followed by CREB activation was the major regulator of increased SPHK2 transcription in FCS(−) culture. EMSA and ChIP assay confirmed the direct binding of activated CREB to the CREB binding site of 5′ SPHK2 promoter region. Colon cancer cells examined continued to grow in FCS(−) culture, although mildly, while hypoxia and glucose depletion suppressed cell proliferation or induced cell death, suggesting the different role of SPHK2 in different stress conditions. Because of the unique relationship observed after serum depletion, we examined effects of siRNA for SPHK2, and found the role of SPHK2 as a growth or survival factor but not a cell proliferation inhibitor in FCS(−) culture. J. Cell. Biochem. 116: 2227–2238, 2015. © 2015 Wiley Periodicals, Inc.</jats:p></jats:sec>
収録刊行物
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- Journal of Cellular Biochemistry
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Journal of Cellular Biochemistry 116 (10), 2227-2238, 2015-08-14
Wiley
