| Project/Area Number |
16591614
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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 |
Urology
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| Research Institution | FUKUOKA PREFECTURAL UNIVERSITY |
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Principal Investigator |
MORIYAMA Nobuo FUKUOKA PREFECTURAL UNIVERSITY, Experimantal Nursing, Professor, 教授 (80143501)
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| Co-Investigator(Kenkyū-buntansha) |
SEKI George The University of Tokyo, Urology, Assistant Professor, 医学部附属病院, 講師 (30206619)
ARIIZUMI Takashi FUKUOKA PREFECTURAL UNIVERSITY, Experimantal Nursing, Asociate Professor, 看護学部, 助教授 (30286166)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | kidney / renal cell carcinoma / Na-HCO_3-cotransporter / motility of the RCC cells / inhibitors of NBC1 / anti NBC1 ribozime / NBC1特異的阻害剤(S0859) / 抗NBC1リボザイム(Rz-NBC1) / NBC1 / 腎癌細胞転移 / 細胞内pH |
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| Research Abstract |
Na-HCO^<3-> cotransporter (NBC-1) plays an essential role in the whole-body acid-base balance as well as the maintenance of homeostasis in several tissues. NBC1 has two variants, kNBC1 from kidney and pNBC1 from pancreas. We have previously identified that kNBC1 is expressed in the basolateral membrane of human renal proximal tubules. We have also identified that kNBC1 is expressed in renal carcinoma cells (RCC).
The purpose of this study was to clarify the role of NBC1 in RCC. In several RCC cell lines of human origin, we identified that both kNBC1 and pNBC1 are expressed. By measurement of cell pH, we also showed that the transport activity of NBC1 is present in these cells. In Boyden-chamber experiments, we confirmed that inhibitors of NBC1 strongly inhibited the motility of these cells. In contrast to other cancer cells, however, the inhibitors of Na/H exchanger did not inhibit the motility, suggesting the unique dependency of RCC motility on NBC1 activity. We also confirmed the similar role of NBC1 in RCC cell from mice. Using these RCC cells, we are now trying to establish the cell lines which have reduced or enhanced NBC1 expression.
On the other hand, we also showed that in rat kidney both kNBC1 and pNBC1 are expressed in proximal tubules. While kNBC1 is expressed in the basolateral membranes, pNBC1 is expressed in the apical membranes. Since the induction of academia did not change the localization of pNBC1, however, pNBC1 is unlikely to play a major role in acid/base balance.
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