2005 Fiscal Year Final Research Report Summary
In vivo analysis of Helicobacter pylori induced stomach cancers
| Project/Area Number |
16590335
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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 |
Experimental pathology
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
TSUKAMOTO Tetsuya Aichi Cancer Center Research Institute, Division of Oncological Pathology, Section Head, 腫瘍病理学部, 室長 (00236861)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Stomach cancer / Helicobacter pylori / Intestinal metaplasia / Gastric type / Intestinal type / Transcription factor / beta-catenin / Wnt |
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| Research Abstract |
Helicobacter pylon has been revealed to be an important factor for gastric carcinogenesis. We have analyzed association of gastric and intestinal phenotypic expression and alteration of oncogenes and tumor suppressor genes in stomach cancers developed in human cases as well as rodent models.
1. Stomach cancers were classified into (1) gastric (G) type, expressing MUC5AC (mucin core protein localized in foveolar epithelium) or MUC6 (in pyloric gland cells), (2) intestinal (I) type, harboring MUC2 in intestinal goblet cells or villin on brush border, (3) gastric-and-intestinal mixed (GI) type, harboring both G and I types, and (4) null (N) type, possessing none of them.
2. Sox2 was found to be transcribed in G and GI-mixed type adenocarcinomas in accordance with MUC5AC and MUC6 expression, while Cdx1 and Cdx2 were up-regulated in GI-mixed and I types along with the expression of MUC2 and villin. In the N type, both gastric and intestinal transcription factors were suppressed. Immunohistochemistry confirmed expression of Sox2 in MUC5AC+ lesions and Cdx2 localization together with MUC2.
3. Thirteen (18.6%) advanced and 5 (16.7%) intramucosal gastric cancers were judged to be hMLH1-negative. In the intramucosal cases, MUC5AC expression was observed in all 5 hMLH1-negative differentiated-type cancers, showing the association of gastric phenotype and microsatellite instability
4. Seventy-seven regions in 39 stomach adenocarcinomas were evaluated according to the beta-catenin localization and gastric and intestinal phenotypes. The cases of nuclear beta-catenin localization showed increase from G to I types. Molecular analysis of beta-catenin and APC genes revealed 10 tumors to be heterogeneous out of 16 informative cases (62.5%).
5. The clinicopathological significance of colonic and small-intestinal phenotypes has hitherto remained unclear in gastric cancers. Of 86 gastric cancers, sucrase and CA1 expression was observed in 12 (14.0%) and only in two cases (2.3%), respectively.
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Research Products
(40 results)
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[Journal Article] High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk.2006
Author(s)
Maekita, T., Nakazawa, K., Mihara, M., Nakajima, T., Yanaoka, K., Iguchi, M., Arii, K., Kaneda, A., Tsukamoto, T., Tatematsu, M., Tamura, G., Saito, D., Sugimura, T., Ichinose, M., Ushijima, T.
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Journal Title
Clin Cancer Res 12
Pages: 989-995
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gastric and intestinal phenotypes and histogenesis of advanced glandular stomach cancers in carcinogen-treated, Helicobacter pylori-infected Mongolian gerbils.2006
Author(s)
Mizoshita, T., Tsukamto, T., Takenaka, Y., Cao, X., Kato, S., Kaminishi, M., Tatemastu, M.
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Journal Title
Cancer Sci 97
Pages: 38-44
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils.2005
Author(s)
Magari, H., Shimizu, Y., Inada, K.I., Enomoto, S., Tomeki, T., Yanaoka, K., Tamai, H., Arii, K., Nakata, H., Oka, M., Utsunomiya, H., Tsutsumi, Y., Tsukamoto, T., Tatematsu, M., Ichinose, M.
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Journal Title
Biochem.Biophys.Res.Commun. 334
Pages: 606-612
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Microsatellite instability is linked to loss of hMLH1 expression in advanced gastric cancers : lack of a relationship with the histological type and phenotype.2005
Author(s)
Mizoshita, T., Tsukamoto, T., Cao, X., Otsuka, T., Ito, S., Takahashi, E., Nakamura, S., Nakamura, T., Yamamura, Y., Tatematsu, M.
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Journal Title
Gastric Cancer 8
Pages: 164-172
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Colonic and small-intestinal phenotypes in gastric cancers : Relationships with clinicopathological findings.2005
Author(s)
Mizoshita, T., Tsukamoto, T., Tanaka, H., Takenaka, Y., Kato, S., Cao, X., Joh, T., Tatematsu, M.
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Journal Title
Pathol.Int. 55
Pages: 611-618
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mixed gastric- and intestinal-type metaplasia Is formed by cells with dual intestinal and gastric differentiation.2005
Author(s)
Niwa, T., Ikehara, Y., Nakanishi, H., Tanaka, H., Inada, K., Tsukamoto, T., Ichinose, M., Tateatsu, M.
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Journal Title
J.Histochem.Cytochem. 53
Pages: 75-85
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Coexistence of gastric- and intestinal-type endocrine cells in gastric and intestinal mixed intestinal metaplasia of the human stomach.2005
Author(s)
Otsuka, T., Tsukamoto, T., Mizoshita, T., Inada, K., Takenaka, Y., Kato, S., Yamamura, Y., Miki, K., Tatematsu, M.
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Journal Title
Pathol.Int. 55
Pages: 170-179
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of small intestinal and colonic phenotypes in complete intestinal metaplasia of the human stomach.2005
Author(s)
Tanaka, H., Tsukamoto, T., Mizoshita, T., Inada, K., Ogasawara, N., Cao, X., Kato, S., Joh, T., Tatematsu, M.
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Journal Title
Virochows Arch 447
Pages: 806-815
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Sox2 expression in human stomach adenocarcinomas with gastric and gastric-and-intestinal-mixed phenotypes.2005
Author(s)
Tsukamoto, T., Mizoshita, T., Mihara, M., Tanaka, H., Takenaka, Y., Yamamura, Y., Nakamura, S., Ushijima, T., Tatematsu, M.
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Journal Title
Histopathology 46
Pages: 649-658
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Beta-catenin gene alteration in glandular stomach adenocarcinomas in N-methyl- N-nitrosourea-treated and Helicobacter pylori-infected Mongolian gerbils.2004
Author(s)
Cao, X., Tsukamoto, T., Nozaki, K., Mizoshita, T., Ogasawara, N., Tanaka, H., Takenaka, Y., Kaminishi, M., Tatematsu, M.
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Journal Title
Cancer Sci. 95
Pages: 487-490
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Eradication of Helicobacter pylori induces apoptosis and inhibits proliferation of heterotopic proliferative glands in infected Mongolian gerbils.2004
Author(s)
Cao, X., Tsukamoto, T., Nozaki, K., Shimizu, N., Mizoshita, T., Kumagai, T., Kaminishi, M., Tatematsu, M.
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Journal Title
Cancer Sci. 95
Pages: 872-877
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers.2004
Author(s)
Kaneda, A., Wakaznono, K., Tsukamoto, T., Watanabe, N., Yagi, Y., Tatematsu, M., Kaminishi, M., Sugimura, T., Ushijima, T.
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Journal Title
Cancer Res. 64
Pages: 6410-6415
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of the intestine-specific transcription factors, Cdx1 and Cdx2, correlates shift to an intestinal phenotype in gastric cancer cells.2004
Author(s)
Mizoshita, T., Inada, K., Tsukamoto, T., Nozaki, K., Joh, T., Itoh, M., Yamamura, Y., Ushijima, T., Nakamura, S., Tatematsu, M.
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Journal Title
J.Cancer Res.Clin.Oncol. 130
Pages: 29-36
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Immunohistochemically detectable Cdx2 is present in intestinal phenotypic elements in early gastric cancers of both differentiated and undifferentiated types, with no correlation to non-neoplastic surrounding mucosa.2004
Author(s)
Mizoshita, T., Tsukamoto, T., Inada, K., Ogasawara, N., Hirata, A., Kato, S., Joh, T., Itoh, M., Yamamura, Y., Tatematsu, M.
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Journal Title
Pathol.Int. 54
Pages: 392-400
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Down regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2:Inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia.2004
Author(s)
Tsukamoto, T., Inada, K., Tanaka, H., Mizoshita, T., Mihara, M., Ushijima, T., Yamamura, Y., Nakamura, S., Tatematsu, M.
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Journal Title
J.Cancer Res.Clin.Oncol. 130
Pages: 135-145
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] High salt diets dose-dependently promote gastric chemical carcinogenesis in Helicobacter pylon-infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells.
Author(s)
Kato, S., Tsukamoto, T., Mizoshita, T., Tanaka, H., Kumagai, T., Ota, H., Katsuyama, T., Asaka, M., Tatematsu, M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mutations and nuclear accumulation of beta-catenin correlate with intestinal phenotypic expression in human stomach cancer.
Author(s)
Ogasawara, N., Tsukamoto, T., Mizoshita, T., Inada, K., Cao, X., Takenaka, Y., Joh, T., Tatematsu, M.
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Journal Title
Histopathology (in press)
Description
「研究成果報告書概要(欧文)」より
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