| Project/Area Number |
15590656
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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 | Kochi Univasity |
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Principal Investigator |
NISHIMORI Isao Kochi Medical School, Department of Gastroenterology and Hepatology, Assocsiate professor, 医学部附属病院, 講師 (30237747)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Tamotsu Kochi Medical School, Department of Pathology, Assistant professor, 医学部, 助手 (50226990)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | carbonic anhydrase / carbonic anhydrase-related protein / intestinal cell of Cajar / gastrointestinal stromal tumor / colon cancer / lung cancer / invasion / proliferation / マクロアレイ / 炭素脱水酵素 / 炭素脱水酵素関連蛋白 / CA-RP / GIST |
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| Research Abstract |
Among the carbonic anhydrase(CA) gene family, CA-related proteins(CA-RP) were investigated for the effect on proliferation and invasion properties of colon cancer, gastrointestinal stromal tumor(GIST), and also lung cancer.
1.Ectopic expression of CA-RP VIII by cDNA transfection in the cultured colon cancer cells (Lovo) increased proliferation and invasion properties compared to wild-type Lovo, which were shown by MTT assay and by using chemotaxis chambers.
2.Xenograft produced by injection of ectopically CA-RP VIII-expressed Lovo into mice (6 weeks-old female, n=5) showed increased tumor growth rate compared to that of wild-type Lovo (p<0.05).
3.Immunohistochemical analysis in GIST tissue specimens (n=26) showed positive staining for CA-RP VIII in 14 cases (54%), for CA-RP X in none and for CA-RP XI in 24 cases (92%). Otherwise, intestinal cell of Cajar that has been believed to develop to GIST showed no expression of all three CA-RPs.
4.Ectopic expression of CA-RP XI by cDNA transfection in the cultured GIST cells (GIST-T1) increased proliferation and invasion properties compared to wild-type GIST-T1, which were shown by MTT assay and by using chemotaxis chambers.
5.Immunohistochemical analysis for expression of CA-RP VIII showed weak staining in bronchial ciliated cells in normal lung. Otherwise, 75% of squamous cell carcinoma (n=24) and 68% of adenocarcinoma (n=25) showed strong expression of CA-RP VIII, especially in the marginal area of the tumors.
6.Ectopic expression of CA-RP VIII by cDNA transfection in the cultured lung cancer cells (PC9) increased proliferation property compared to wild-type PC9.
These findings suggest CA-RPs VIII and XI function to enhance proliferation and invasion in gastrointestinal tumor cells. Similar results were observed in lung cancer cells, indicating that the finings is commonly observed during carcinogenesis.
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