2004 Fiscal Year Final Research Report Summary
The mechanism of the development of gastric-and-intestinal mixed intestinal metaplasia-the analysis of homeobox genes in the isolated pyloric glands-
| Project/Area Number |
15390121
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Aichi Cancer Center |
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Principal Investigator |
TATEMATSU Masae Aichi Cancer Center, Division of Oncological Pathology, Chief, 腫瘍病理学部, 副所長兼部長 (70117836)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAMOTO Tetsuya Aichi Cancer Center, Division of Oncological Pathology, Section head, 腫瘍病理学部, 室長 (00236861)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Homeobox genes / Phenotype / Sox2 / Cdx1 / 2 / gastric-and-intestinal mixed phenotype / intestinal metaplasia / gastric cancers / human defensin-5 |
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| Research Abstract |
Intestinal metaplasia(IM) has been extensively studied as a possible premalignant condition in the human stomach. However, many questions remain regarding the pathogenesis of IM development as well as its relationship to gastric cancers. Homeobox genes are very important for the development and maintenance of the organs. In this study, we evaluated the relation between the phenotypes and gastric and intestinal specific transcription factors in IM glands and gastric cancers. The expression of Sox2 as a gastric specific transcription factor was strongly associated with the gastric phenotypic expression such as MUC5AC and MUC6,while Cdx1/Cdx2 as intestinal specific transcription factors had a close relation to intestinal phenotypic expression as MUC2 and villin in both IM glands and gastric cancers. The expression of Sox2 decreased from gastric (G), through gastric-and-intestinal-mixed (GI), to the intestinal (I) phenotypes, while Cdx1/2 were inversely correlated in both IM glands and gastric cancers, independent of the histological types. Cdx2 positive groups had a significant better survival than the negative ones in the advanced gastric cancers. Human defensin-5(HD-5) was a useful Paneth cell differentiation marker, and Paneth cell differentiation of gastric cancer cells did not occur alone, but was accompanied by intestinalization of gastric cancer tissues. Double staining revealed coexistence of MUC5AC- and MUC2/villin/CD10-immunoreactivity in the same cell in GI-IM glands. In conclusions, our results suggest that the expression of gastric and intestinal specific genes is very important for the phenotypic expression of both IM glands and gastric cancer cells. In addition, Cdx2 is a useful prognostic and intestinal phenotypic marker in the advanced gastric cancers. IM may be due to abnormal stem cell differentiation still obeying a certain order.
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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., Tatematsu, 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] Down regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdxl 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] 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., Job, 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] Expression of the intestine-specific transcription factors, Cdxl and Cdx2, correlates shift to an intestinal phenotype in gastric cancer cells.2004
Author(s)
Mizoshita, T., Inada, K., Tsukamoto, T., Nozaki, K., Job, 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] 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] beta-Catenin mutations and nuclear accumulation during progression of rat stomach adenocarcinomas.2003
Author(s)
Tsukamoto, T., Yamamoto, M., Ogasawara, N., Ushijima, T., Nomoto, T., Fujita, H., Matsushima, T., Nozaki, K., Cao, X., Tatematsu, M.
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Journal Title
Cancer Sci 94
Pages: 1046-1051
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of Cdx2 and the phenotype of advanced gastric cancers: relationship with prognosis.2003
Author(s)
Mizoshita, T., Tsukamoto, T., Nakanishi, H., Inada, K., Ogasawara, N., Joh., T., Itoh, M., Yamamura, Y., Tatematsu, M.
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Journal Title
J Cancer Res Clin Oncol 129
Pages: 727-734
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.
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 (in press)
Description
「研究成果報告書概要(欧文)」より
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