| Project/Area Number |
18500330
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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 |
Laboratory animal science
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| Research Institution | Juntendo University |
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Principal Investigator |
ZHANG Danqing Juntendo University, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR (40296877)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Toshiyuki JUNTENDO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR (40260070)
HINO Okio JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR (90127910)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Erc / Mesothelin gene / Tsc2 gene / GPI anchor protein / knockout mouse / Carcinogenesis / Erc遺伝子 |
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| Research Abstract |
The Erc (expressed in renal carcinoma) was identified as an inducible gene during the renal carcinogenesis of the Eker (Tsc2 mutant) rat and is a homologue of the human Mesothelin gene. Erc is also overexpressed in the renal carcinoma cell line of the Tsc2 knockout (KO) mouse. To elucidate functional importance of Erc in renal carcinogenesis as well as in mesothelioma, we have performed genetic cross experiments between Tsc2 KO and Erc KO mice. Then we examined influence of the Erc genotype on the development of renal carcinomas in the Tsc2 hetero-mutant mouse. In 32% of male and 20% of female Tsc2 hetero-mutant mice with wild-type Erc, renal carcinomas with a diameter ranging from 4 to 30mm were developed by the age of 18 months. In contrast, all of the renal carcinomas in Tsc2 hetero-mutant mice with Erc homo-mutation had a diameter equal to or less than 2mm. There was no remarkable difference in the size of renal tumors between Tsc2 hetero-/Erc hetero-mutant and Tsc2 hetero-mutant/Erc wild-type mice. These results suggest that Erc may play an important role for tumor proliferation. In addition, we established Tsc2/Erc-deficient renal carcinoma cell lines and then transferred Erc-expression system into them. Adhesion of cell lines to the collagen-coated plate became stronger by overexpression of Erc protein. On the other hand, cell adhesive property was deteriorated when Erc expression was inhibited by RNA interference, suggesting that Erc has a role in the cell-substrate adhesion. Now we are further investigating in vivo function of Erc by implanting the renal carcinoma cell lines into the nude mouse.
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