| Project/Area Number |
11470265
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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 |
Digestive surgery
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| Research Institution | Kansai Medical University |
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Principal Investigator |
YAMAMICHI Keigo (2001) Kansai Medical University, Faculty of Medicine, Lecturer, 医学部, 講師 (70291804)
日置 紘士郎 (1999-2000) 関西医科大学, 医学部, 学長 (60077641)
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| Co-Investigator(Kenkyū-buntansha) |
IKENAKA Kazuhiro Okazaki National Research Institutes, Laboratory of Neural Information, Professor, 神経情報, 教授 (00144527)
NAKANE Yasushi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60155778)
OKUMURA Syunichiro Kansai Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (00319617)
山道 啓吾 関西医科大学, 医学部, 講師 (70291804)
大草 世雄 関西医科大学, 医学部, 助手 (80247907)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | gastric cancer / cancer associated gene / functional cloning / retrovirus vector / 機能発現クローニング / レトロウイルスベクター |
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| Research Abstract |
The present study was directed towards the identification of novel factors involved in the transformation process leading to the formation of gastric cancer. A cDNA library from human gastric cancer cells was constructed using a retrovirus vector. Functional cloning was performed by screening for transformation activity in transduced NIH3T3 cells. A total of 6 cDNA clones were isolated, including one encoding the elongation factor 1α subunit which has already been known to play a role in tumorigenesis. One cDNA (clone 56.2), which was repeatedly isolated during the course of screening, encoded a protein identical to a G-protein-coupled receptor protein, GPR35. In addition, another cDNA clone (72.3) was found to be an alternatively spliced product of the GPR35 gene, whereby an additional 31 amino acids were added to the N-terminus of GPR35. Hence, the proteins encoded by clones 56.2 and 72.3 were designated GPR35a and GPR35b, respectively. RT-PCR experiments revealed that GPR35 gene expression is low or absent in the surrounding non-cancerous regions, while both mRNAs were present in all of the gastric cancers examined. The level of 72.3 encoded mRNA was consistently significantly higher than that of 56.2 encoded mRNA. An expression pattern similar to that observed in gastric cancers was detected in normal intestinal mucosa. Based on the apparent transformation activities of the two GPR35 clones in NIH3T3 cells, and the marked up-regulation of their expression levels in cancer tissues, it is speculated that these two novel isoforms of GPR35 play significant roles during the course of gastric cancer formation.
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