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The role of Na-HCO_3 cotransporter in metastasis of renal cell carcinoma

Na-HCO_3协同转运蛋白在肾细胞癌转移中的作用

基本信息

批准号：
14571486
负责人：
MORIYAMA Nobuo
金额：
$ 1.92万
依托单位：
Fukuoka Prefectural University (2003)The University of Tokyo (2002)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

The Na^+-HCO<3-> cotransporter (NBC-1) plays a major role in bicarbonate absorption from proximal tubules. However, which NBC-1 variant mediates proximal bicarbonate absorption has not been determined. Moreover, the localization of this cotransporter in human kidney, renal cell carcinoma (RCC) tissues, and rat kidney has not been clarified. To clarify them, immunohistochemical analysis was performed using the specific antibodies against kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters.In Western blot analysis the expression of kNBC-1 but not of pNBC-1 was detected in normal human kidney and RCC tissues. In immunofluorescence analysis on normal renal tissues the anti-kNBC-1 antibody strongly and exclusively labeled the basolateral membranes of proximal tubules. In RCC cells, the anti-kNBC-1 antibody labeled both plasma membranes and intracellular organelles. The labeling by anti-pNBC-1 antibody was not detected in both normal kidney and RCC tissues.Then, we determined the localization of NBC-1 variants in rat kidney. In Western blot analysis of rat kidney both anti-kNBC-1 and anti-pNBC-1 antibodies yielded a 130 kDa band. In immunohistochemical analysis the anti-kNBC-1 antibody produced a strong and exclusively basolateral labeling in proximal tubules. On the other hand, the occasional pNBC-1 labeling was detected in the apical membranes of proximal tubules. The basolateral localization of kNBC-1 as well as the localization of pNBC-1 on the basis of the brush border was further supported by electron microscopic observation.These results are consistent with a view that kNBC-1 is the dominant variant that mediates bicarbonate reabsorption from human and rat renal proximal tubules. They also suggest that NBC-1 may have distinct roles in cancer cells.

Na^+-HCO<3->协同转运蛋白（NBC-1）在近端小管吸收碳酸氢盐的过程中起主要作用。然而，哪种NBC-1变体介导近端碳酸氢盐吸收尚未确定。此外，这种协同转运蛋白在人肾、肾细胞癌（RCC）组织和大鼠肾中的定位尚未阐明。免疫组化检测肾型转运蛋白（kNBC-1）和胰腺型转运蛋白（pNBC-1）的表达，Western blot检测正常肾组织和肾癌组织中kNBC-1的表达，而pNBC-1的表达不明显。在对正常肾组织的免疫荧光分析中，抗kNBC-1抗体强烈且专门标记近端小管的基底外侧膜。在RCC细胞中，抗kNBC-1抗体标记质膜和细胞内细胞器。抗pNBC-1抗体在正常肾组织和肾细胞癌组织中均未检测到标记。在大鼠肾脏的Western印迹分析中，抗kNBC-1和抗pNBC-1抗体均产生130 kDa条带。在免疫组织化学分析中，抗kNBC-1抗体在近端小管中产生强烈且仅基底外侧标记。另一方面，偶见pNBC-1标记在近端小管的顶膜。kNBC-1的基底外侧定位以及刷状缘的基础上的pNBC-1的本地化进一步得到支持的电子显微镜observation.These结果是一致的观点，即kNBC-1是介导的重吸收从人类和大鼠肾近端小管的碳酸氢盐的优势变体。他们还表明NBC-1可能在癌细胞中具有不同的作用。