2004 Fiscal Year Final Research Report Summary
INVOLVEMENT OF THE INACTIVATION OF DNA MISMATCH REPAIR SYSTEM ON THE CELLULAR IMMORTALIZATION MECHANISMS OF HUMAN GASTROINTESTINAL CANCERS.
| Project/Area Number |
14370070
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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 | Kobe University |
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Principal Investigator |
YOKOZAKI Hiroshi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10200891)
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| Project Period (FY) |
2002 – 2004
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| Keywords | GASTRIC CANCER / COLORECTAL CANCER / CELLULAR IMMORALIZATION / DNA MISMATCH REPAIR SYSTEM / TELOMERE / TELOMERASE / DNA RECOMBINATION / APOPTOSIS |
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| Research Abstract |
The purposes of the present research project were to clarify the mechanism of telomere maintenance, escapement mechanism from apoptosis through DNA mismatch repair defect and the rote of mismatch repair defect on the cellular immortalization of gastrointestinal cancers. The results obtained during the term were as following.
Human gastric and colorectal cancers were subclassified according to the microsatellite status and p53 immunoreactivity as mutator-type (tumors with microsatellite instability (MSI)), suppressor/p53-type (mirosatellite stable (MSS) tumors with strong p53 expression or loss of heterozygosity at D17S250 (p53 locus) and unclassified (the other MSS tumors).
1.Mutator-type gastric mucinous adenocarcinomas showed lower proliferative activity and better prognosis in comparison with other types. They also revealed the infrequent immunoreactivity to CD10, a marker for the brush-border of enterocytes. Mutator-type colorectal mucinous adenocarcinomas demonstrated significantly frequent immunoreaction to HGM, a gastric mucin marker, and had tendency to locate at proximal colon, while suppressor/p53-type tumors showed frequent venous infiltration and lymph node metastasis with higher clinicopathological stage. These indicated that mucinous carcinomas of the gastrointestinal tract might be subuclassified molecular pathologically.
2.Infrequent expression of h TERT mRNA, a catalytic subunit of telomerase, was observed in mutator-type tumors in comparison with other subtypes when 208 cases of colorectal carcinomas were analyzed by in situ hybridization, suggesting that reactivation of telomerase might be a rare event in MSI colorectal carcinomas with telomerase independent cellular immortalization.
3.A system for telomere length quantification on paraffin-embedded pathologrcal specimens was established during the term of the research project.
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