| Project/Area Number |
15590618
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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 |
Gastroenterology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SHODA Junichi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (90241827)
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| Co-Investigator(Kenkyū-buntansha) |
川本 徹 筑波大学, 臨床医学系, 講師 (30282354)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | gallbladder carcinoma / animal model / mucin glycoprotein / oncogene / signal transduction / gallbladder carcinogenesis / 実験リトル |
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| Research Abstract |
The overall prognosis of gallbladder carcinoma is poor because of a high percentage of advanced cases at the time of operation and thereby a lower curability. pT2 carcinoma is limited in the gallbladder wall, and therefore a high curability as well as a better prognosis can be expected. However, the prognosis has not been necessarily good since distant recurrences are found in some cases of pT2 carcinomas. Alterations in glycosilation of mucins, such as an alteration in the site of O-glycosylation of mucin core proteins or an enhanced sialylation of carbohydrate structures, are known in the process of malignant transformation.
Mucin-type O-glycosilation is initiated by GalNAc-T isozymes and O-glycosilation in adenocarcinoma cell lines is reportedly catalyzed by GalNAc-T3. In pT2 gallbladder carcinoma, the differential expression of GalNAc-T3 in pT_2 carcinoma may modulate the malignant behavior of the carcinoma cells by affecting the biological properties of mucins due to the altered O-
… More
glycosilation.
Sialylated MUC1 recognized by a mAb MY.1E12 (Jpn J Cancer Res 1996;87:488-496) has been used as a marker for invasive adenocarcinomas. In pT2 gallbladder carcinoma, the high level expression of stromal localization of sialylated MY. 1E12-reactive-MUC1 at the invading sites correlates with the aggressiveness of the disease, such as the tendency to form distant metastasis.
BK5.ErbB2 transgenic mice overexpressing erbB2 develop gallbladder carcinoma at a high incidence. Recently, Muc4 (sialomucin complex) has been shown to influence erbB2 (tyrosine kinase) activity through direct interaction with the receptor and to potentiate tumor growth in mammalian carcinoma cells. Also in the transgenic mice, up-regulation of Muc4 and its interaction with erbB2 may be involved in the process of gallbladder carcinogenesis through modulation of phosphorylation of the receptor tyrosine kinase.
Thus, alterations in carbohydrate chains of carcinoma-producing mucin glycoproteins potentiate the capability of tumor invasion and/or metastasis and Muc4 may play an important role in gallbladder carcinogenesis through the activation of erbB2. Less
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