| Project/Area Number |
12470329
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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 |
Urology
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
TOMITA Yoshihiko Department : Graduate School of Medical and Dental Sciences, NIIGATA UNIVERSITY, associate professor, 大学院・医歯学総合研究科, 助教授 (90237123)
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| Co-Investigator(Kenkyū-buntansha) |
OBARA Kenji Medical Hospital, NIIGATA UNIVERSITY, assistant, 医学部・附属病院, 助手 (70313533)
TANIKAWA Toshik Medical Hospital, NIIGATA UNIVERSITY, Lecturer, 医学部・附属病院, 講師 (70236686)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | p14^<ARF> / renal cell carcinoma / transcription / 膀胱癌 |
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| Research Abstract |
p19^<ARF> (p14^<ARF> in human) binds and inhibits MDM2 function leading to sound function of p53 as a guardian of genome. In this project we have investigated gene status and function of p14^<ARF> in Urological tumors, and obtained results as follows :
1. Among transitional cell cancer cell lines, RT4 did not have mRNA suggesting homozygous deletion (HD).
2. Out of 4 renal cell carcinoma (RCC) cell lines, ACHN and KRC/Y expressed p14^<ARF> mRNA.
3. Using quantitative DNA-PCR evaluating HD, 3 RCC cell lines were suggested to have HD.
4. Immunihistochemical staining for p14^<ABF> using 3 different antibodies, no positive staining was detected in RCC samples.
5. Eight of thirty-four DNA extracted for tumor specimens revealed HD pattern and also poorer prognosis.
6. Introduction of p14^<AEF> gene in deficient cell lines resulted in lethal, and one stable transfectant showing p14^<ARF> mRNA positivity did not have any protein, indicating presence of epigenetic mechanism inactivating p14^<AHF> function. Thus, RCC showing infrequent p53 gene alteration may carry malfunction of p14^<ARF> because of HD or inactivation by epigenetical mechanism(s).
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