1999 Fiscal Year Final Research Report Summary
Research on the abnormal expressions of bcl-xL and bak in gastrointestinal cancers
| Project/Area Number |
10670470
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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 | Osaka University |
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Principal Investigator |
KANAYAMA Shuji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40185913)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Yoshiji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30303960)
SHINOMURA Yasuhisa Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Gastric cancer / Colorectal cancer / Apoptosis / bcl-xL / bak / Missence mutation / IRF-1 / Stat3 |
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| Research Abstract |
The present research was designed to clarify how bcl-xL and bak are regulated in the gastrointestinal cancers.
Levels of bcl-xL, bak, IRF-1 and IRF-2 mRNAs were determined by a reverse transcription-polymerase chain reaction in endoscopic biopsy specimens from gastric and colorectal cancers. Enhanced expression of bcl-xL and reduced expression of bak were demonstrated in both gastric and colorctal cancers. In the colorectal cancers, expression of IRF-1 mRNA was significantly decreased. This decrease in the IRF-1 mRNA was negatively and positively correlated with bcl-xL and bak mRNAs, respectively. On the other hand, in the gastric cancers, no significant correlations were observed among their mRNA expressions. Abnormal expression of IRF-2 mRNAs were not observed in the gastric and colorctal cancers examined. These results suggest that abnormal regulation of bcl-xL and bak expressions are relevant to reduced expression of IRF-1 in colorectal cancers.
The oncogenic ras mutation is a common
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and critical step in gastrointestinal carcinogenesis. Oncogenic rastransfected intestinal epithelial cells showed an apoptosis resistance with Stat3 activation and bcl-xL increase.
The possible mutation of bak gene could play a significant role in the apoptosis resistance of cancers. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire cording lesion of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early and 18 advanced cancers) and 20 primary colorectal cancers (6 early and 14 advanced cancers). Missense bak gene mutations were observed in 3 of 24 (12.5%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Sequence alterations without amino acid alteration were observed 1 of 24 (4.2%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Mutations in the bak gene were observed only in advanced gastrointestinal cancers but not in early stage carcinomas. These observations suggest that mutations in this gene predispose to the development of gastrointestinal malignancies in, at least, a subset of the cases. Less
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Research Products
(14 results)
