2007 Fiscal Year Final Research Report Summary
Regulation of Wnt signaling pathway by galectin-3 in hepato-biliary-pancreatic cancer : Special reference to mutation of galectin-3
| Project/Area Number |
16591291
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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 |
Digestive surgery
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| Research Institution | Gunma University |
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Principal Investigator |
SHIMURA Tatsuo Gunma University, Faculty of Medicine, Assistant Professor (00282393)
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| Co-Investigator(Kenkyū-buntansha) |
TSUTSUMI Souichi Gunma University, Graduate school of Medicine, Assistant Professor (30323356)
ASAO Takayuki Gunma University, Graduate school of Medicine, Associate Professor (40212469)
KUWANO Hiroyuki Gunma University, Graduate school of Medicine, Professor (90186560)
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| Project Period (FY) |
2004 – 2007
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| Keywords | galectin-3 / Wnt / Hepato-Biliary-Pancreatic cancer / gastrointestinal malignancy |
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| Research Abstract |
Galectin-3 (gal-3), a pleiotrophic protein, is an important regulator of tumor metastasis, which like beta-catenin shuttles between the nucleus and the cytosol in a phosphorylation-dependent manner. We report herein that beta-catenin stimulation of cyclin D1 and c-myc expression is gal-3 dependent. Gal-3 binds to beta-catenin/Tcf complex, colocalizes with beta-catenin in the nucleus, and induces the transcriptional activity of Tcf-4 as determined by the TOP/FOPFLASH reporter system. We have identified the beta-catenin gal-3-binding sequences, which are in the NH2 and COOH termini of the proteins encompassing amino acid residues 1 to 131 and 143 to 250, respectively. These data indicate that gal-3 is a novel binding partner for beta-catenin involved in the regulation of Wnt/beta-catenin signaling pathway.
Analysis of the human gal-3 sequence reveled a structural similarity to beta-catenin as it also contains the consensus sequence (S92XXXS96) for glycogen synthase kinase-3beta (GSK-3beta
… More
) phosphorylation and can serve as its substrate. In addition, Axin, a regulator protein of Wnt that complexes with beta-catenin, also binds gal-3 using the same sequence motif identified here by a deletion mutant analysis. The data presented here give credence to the suggestion that gal-3 is a key regulator in the Wnt/beta-catenin signaling pathway and highlight the functional similarities between gal-3 and beta-catenin.
Gal-3 and Ki-67 expressions were assessed by immunohistochemistry in 115 patients with gastric cancer. PCR-single strand conformation polymorphism (SSCP)-sequence analysis and the levels of gal-3 mRNA were also examined. The present study demonstrated that gal-3 expression was correlated with nodal status, lymphatic inivasion, pathological stage and histological parameters. On the other hand, gal-3 expression did not correlate with the expression of Ki-67. Reduced expression of gal-3 was significantly associated with a poor prognosis and multivariate analysis showed that gal-3 expression was an independent prognostic factor. On PCR-SSCP-sequence analysis, 2 single nucleotide polymorphisms (SNPs) were detected in the gal-3 gene, but none showed mutations. Reduced gal-3 expression was associated with lymph node metastasis, advanced stage and tumor differentiation in gastric cancer. Gal-3 expression could be a useful prognostic factor in gastric cancer.
Immunohistochemical assessment of galectin-3, beta-catenin and Ki-67 expression was performed on samples from 108 patients with colorectal cancer. The expression of galectin-3 was classified at the tumor surface and the invasive front, and its relationship with clinicopathological factors was considered from a statistical viewpoint. There was significant liver metastasis when the expression of galectin-3 was lower at the invasive front of a tumor compared to its surface (p = 0.04). There were also significant correlations between beta-catenin expression at the tumor surface and liver metastasis and tumor stage (p=0.03, p=0.04 respectively). The reduction of galectin-3 expression in tumor invasion, metastasis and proliferation in patients with colorectal cancer is suggested. Less
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Research Products
(64 results)
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[Journal Article] Primary liver cancers with nonalcoholic steatohepatitis2007
Author(s)
Hashizume H, Sato K, Takagi H, Hirokawa T, Kojima A, Sohara N, Kakizaki S, Mochida Y, Shimura T, Sunose Y, Ohwada S, Mori M.
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Journal Title
Eur J Gastroenterol Hepatol 19(10)
Pages: 827-34
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Living-related liver transplantation for multiple liver metastases from rectal carcinoid tumor: a case report2006
Author(s)
Nakajima Y, Takagi H, Sohara N, Sato K, Kakizaki S, Nomoto K, Suzuki H, Suehiro T, Shimura T, Asao T, Kuwano H, Mori M, Nishikura K
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Journal Title
World J Gastroenterol 12(11)
Pages: 1805-9
Description
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[Journal Article] Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation2005
Author(s)
Suehiro T, Shimada M, Kishikawa K, Shimura T, Soejima Y, Yoshizumi T, Hashimoto K, Mochida Y, Hashimoto S, Maehara Y, Kuwano H
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Journal Title
Transpl Int 18(8)
Pages: 923-8
Description
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[Journal Article] Cell density modulates the metastatic aggressiveness of a mouse colon cancer cell line, colon 262004
Author(s)
Kuwano H, Miyazaki T, Tsutsumi S, Hirayama I, Shimura T, Mochiki E, Nomoto K, Fukuchi M, Kato H, Asao T.
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Journal Title
Oncology 67(5-6)
Pages: 441-9
Description
「研究成果報告書概要(欧文)」より
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[Presentation] galectin-3-expression in gastric cancer2005
Author(s)
Okada K, Shimura T, Okamura K, Okada T, Hashimoto S, Mochida Y, et. al.
Organizer
The 67th Annual Congress of Japanese Analysis of Surgical Association
Place of Presentation
Tokyo
Year and Date
2005-11-09
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Wnt pathway and galectin-32004
Author(s)
Shimura T, Okada K, Hashimoto S, Kanoh K, Tsutsumi S, Suzuki H, et. al.
Organizer
The 59 Annual Meeting of the Japanese Relationship between Society of the gastroenterological Society
Place of Presentation
Kagoshima
Year and Date
2004-07-21
Description
「研究成果報告書概要(欧文)」より
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