DIVERSITY OF CANCER CELLS CAUSED BY CYTOSINE METHYLATION IN NON-CPG ISLAND
| Project/Area Number |
16590278
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kobe University |
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Principal Investigator |
KITAZAWA Sohei Kobe University, Graduate School of Medicine. Department of Pathology and Microbiology, Division of Pathology, Associate Professor, 大学院医学系研究科, 助教授 (90186239)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Non CpG-island / Methylation / Gene promoter / Bladder cancer / BAMBI / Gene transcription / Pancreatic cancer / TrkA / メチル化 / Desmoid tumor / 神経周囲浸潤 |
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| Research Abstract |
Although global methylation at CpG islands leads to gene silencing, specific methylation at non-CpG islands would play a crucial epigenetic role in the versatility and plasticity of gene expression during cancer progression. We demonstrated the negative cis-acting AP-1-like sequence TGAGCGA in the 5'-untranslated region of the TrkA gene. Steady-state TrkA expression correlated positively with the accumulation of methylated CpG around the AP-1-like site. By EMSA, the AP-1-like site was bound mainly by c-Jun homodimers; the binding was blocked by Sss I-induced methylation. Consequently, activation of TrkA gene expression by methylation was caused by the direct interference of c-Jun binding to the negatively regulating AP-1-like site. Furthermore, methylated CpG around the AP-1-like site was accumulated with increased TrkA expression in cases of advanced pancreatic cancer with extensive perineural invasion.
A rare case of desmoid-type fibromatosis with metaplastic ossification in the chest wall is analyzed. Accumulation of beta-catenin associated with a somatic activating mutation in codon 41 was demonstrated. Bisulfite mapping using microdissected samples showed that BMP and activin membrane-bound inhibitor (BAMBI) expression was specifically downregulated at the ossifying focus due to hypermethylation of its gene promoter. Because both BMP and classical Wnt/beta-catenin/LEF1 signaling cooperatively and mutually induce differentiation of mesenchymal cells into osteoblastic cells and promote bone formation, the epigenetic event leading to the enhanced responsiveness to BMP signaling may play a crucial role in the formation of metaplastic bone.
We have presented our data at various international as well as domestic meetings, and published scientific papers for academic journals.
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Report
(4 results)
Research Products
(77 results)
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[Journal Article] Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency.2007
Author(s)
Takahashi Y, Iida K, Takahashi K, Yoshioka S, Fukuoka H, Takeno R, Imamura M, Nishizawa H, Takahashi M, Seo Y, Hayashi Y, Kondo T, Okimura Y, Kaji H, Kitazawa R, Kitazawa S, Chihara K.
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Journal Title
Gastroenterology 132
Pages: 938-943
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.2006
Author(s)
Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Kasga M.
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Journal Title
J Clin Invest 116
Pages: 1494-1505
Description
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[Journal Article] Estimation of Contrast of Refraction Contrast Imaging Compared with Absorption Imaging -Basic Approach.2005
Author(s)
Hirano M, Yamasaki K, Okada H, Kitazawa S, Kitazawa R, Ohno Y, Sakurai T, Kondoh T, Ohbayashi C, Katafuchi T, Maeda S, Sugimura K, Tamura S.
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Journal Title
Radiat Med 23
Pages: 89-96
NAID
Description
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[Journal Article] A case of MEN type I and menin in parathyroid lesions.2005
Author(s)
Tobimatsu T, Kaji H, Naito J, Yo M, Sowa H, Yamauchi M, Tsukada T, Kitazawa R, Kitazawa S, Sugimoto T, Chihara K.
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Journal Title
Nippon Naibunpitu Gakkai Zassi 81
Pages: 101-103
Description
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[Journal Article] Imaging of fine structure of bone sample with high coherence X-ray beam and high spatial resolution detector.2004
Author(s)
Hirano M, Yamasaki K, Kitazawa R, Kitazawa S, Okada H, Katafuchi T, Maeda S, Sakurai T, Kondoh T, Obayashi C, Sugimura K, Tamura S.
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Journal Title
Radiat Med 22
Pages: 56-59
NAID
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[Journal Article] Overexpression of thioredoxin 1 in transgenic mice suppresses development of diabetic nephropathy.
Author(s)
Hamada Y, Miyata S, Nii-Kono T, Kitazawa R, Kitazawa S, Higo S, Fukunaga M, Ueyama S, Nakamura H, Yodoi J, Fukagawa M, Kasuga M.
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Journal Title
Nephrology Hemodyalysis Transplantation (in press)
Description
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