1996 Fiscal Year Final Research Report Summary
Gene alterations of glycosyltransferase during the course of malignant tranformation in uterine endometrium
| Project/Area Number |
06671685
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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 | Keio University |
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Principal Investigator |
AOKI Daisuke School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (30167788)
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| Co-Investigator(Kenkyū-buntansha) |
UDAGAWA Yasuhiro School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (80118918)
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| Project Period (FY) |
1994 – 1996
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| Keywords | Endometrial cancer / Carbohydrate antigen / Fucosyltransferase / PCR-RFLP / Le gene / Se gene |
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| Research Abstract |
Monoclonal antibody MSN-1 was established against an endometrial cancer cell line and proven to recognize at least Lewis b carbohydrate antigen. Immunohistochemical staining with this antibody resulted in a positive reaction in more than 85% of the endometrial adenocarcinoma cases examined but in few cases with normal endometria, indicating that MSN-1-reactive antigen is able to be a good histochemical marker for endometrial cancers. Expression of the Lewis histo-blood group antigen is determined by the Lewis type alpha (1,3/1,4) fucosyltransferase enconded by the FucT-III gene (Le gene). Since Lewis-negative individuals are known to be homozygous for an allele with missense mutations of this gene (le/le) which cause inactivation of the enzyme activity, we investigated whether or not phenotypic expression of the MSN-1-reactive antigen in endometrial adenocarcinoma specimens was affected by the genotypes of the FucT-III gene in patients with adenocarcinoma. To determine the genotypesof the FucT-III gene, i.e., to detect the mutations, we employed the polymerase chain reaction (PCR) -restriction fragment length polymorphism method by using genomic DNAs extracted from the patients'peripheral blood leucocytes as PCR templates. Out of 59 cases of endometrial adenocarcinoma, four cases with the Lewis-negative genotype (le/le) were identified and examined by the ABC immunohistochemical technique for the presence of the MSN-1-reactive antigen on their cancer cells. The conventional hemagglutination reaction also revealed all four of these cases to have the Lewis-negative blood type. However, their cancer tissues reacted positively with MSN-1. These results suggest that MSN-1 recognizes a fucosylated carbohydrate that is constructed by fucosyltransferases other than FucT-III.
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