2001 Fiscal Year Final Research Report Summary
The functional analysis and clinical significance of apotosis inducing factor, RCAS1
| Project/Area Number |
12671615
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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 |
Obstetrics and gynecology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
SONODA Kenzo Faculty of Medicine, KYUSHU UNIVERSITY, Ass. Professor, 医学部・附属病院, 助手 (30294929)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAKAWA Toshio Faculty of Medicine, KYUSHU UNIVERSITY, Lecturer, 医学部・附属病院, 講師 (20218770)
KOBAYASHI Hiroaki Faculty of Medicine, KYUSHU UNIVERSITY, Ass. Professor, 医学部・附属病院, 助手 (70260700)
KAKU Tsunehisa School of Health Sciences, KYUSHU UNIVERSITY, Professor, 医療技術短期大学部, 教授 (60185717)
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| Project Period (FY) |
2000 – 2001
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| Keywords | tumor associated antigen / apoptosis / lymphocyte / fibroblast / prognostic factor / trophoblast |
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| Research Abstract |
The functional and clinical significance of tumor-associated antigen, RCAS 1, was investigated in this study. RCAS1, one of type II membrane proteins, induces cell apoptosis in normal peripheral lymphocytes. RCAS1 is chromosomally localized to 8q23 and its expression is induced by estrogen. In our previous study, RCAS1 was strongly expressed in uterine and ovarian cancers and the expression of RCAS1 was strikingly correlated with poorprognosis in uterine cancer patients.
(1) In order to clarify a biological role of RCAS1 in tumor behavior, we analyzed an association between RCAS1 expression and tumor stromal cell reaction by immunohistochemistry. In tumor metastatic lymph nodes, the apoptotic index of T lymphocytes significantly increased in uterine cancer patients with RCAS1 expression. In connective tissues surrounded tumor cells, cells with vimentin expression significantly decreased in patients with RCAS1 expression. But the expression of Fas-L or TNF-a was not associated with apoto
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tic index of T lymphocytes, and the number of cells with vimentin expression in connective tissues in the tumor stroma. On the basis of these findings, the expression of RCAS1 plays pivotal factors in the acquirement of tumor aggressiveness through the reduction of immune response and connective tissue reaction.
(2) The relationship between RCAS1 expression and a progression of the uterine endometrial neoplasias was checked, the expression of RCAS1 was statistically higher in adenocarcinoma than in the normal and hyperplastic endometrium. Moreover, RCAS1 was statistically detected more frequently in grade 3 than in grade 1 or 2. These results indicated that RCAS1 expression might be associated with the malignant transformation and poor differentiation observed in uterine endometrial adenocarcinoma.
(3) The involvement ofRCAS1 and Fas-L was studied in the early stage of pregnancy. A reduction in RCAS1 and Fas-L expression was suggested to be closely related with activation and infiltration of maternal NK cells and destruction of uterine glands, resulting in rejection of the fetus. The expression of RCAS1 and Fas-L in the uterine glands and cytotrophoblasts may play a role in the downregulation of the maternal immune response, thereby maintaining pregnancy at early stage.
Our findings demonstrate that RCAS1 plays an important role in the acquirement of tumor aggressiveness. Moreover, RCAS1 might be involved in the maintenance of early pregnancy. Following works are necessary to be done: (1) to identify RCAS1 associated molecules, (2) to clarify molecular mechanisms for RCAS1 induced apoptosis, and (3) to make clear different functions among Fas-L, TNF and RCAS1. Less
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