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蛋白质4.1B/DAL-1在啮齿动物肾上腺髓质中对于嗜铬细胞瘤发生及TSLC1质膜定位的非必需作用

Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1.

作者信息

Ohno Nobuhiko, Terada Nobuo, Komada Masayuki, Saitoh Sei, Costantini Frank, Pace Virgilio, Germann Paul-Georg, Weber Klaus, Yamakawa Hisashi, Ohara Osamu, Ohno Shinichi

机构信息

Department of Anatomy and Molecular Histology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.

出版信息

Biochim Biophys Acta. 2009 Mar;1793(3):506-15. doi: 10.1016/j.bbamcr.2009.01.005. Epub 2009 Jan 20.

Abstract

Protein 4.1B is a membrane skeletal protein expressed in various organs, and is associated with tumor suppressor in lung cancer-1 (TSLC1) in vitro. Although involvement of 4.1B in the intercellular junctions and tumor-suppression was suggested, some controversial results posed questions to the general tumor-suppressive function of 4.1B and its relation to TSLC1 in vivo. In this study, the expression of 4.1B and its interaction with TSLC1 were examined in rodent adrenal gland, and the involvement of 4.1B in tumorigenesis and the effect of 4.1B deficiency on TSLC1 distribution were also investigated using rodent pheochromocytoma and 4.1B-knockout mice. Although plasmalemmal immunolocalization of 4.1B was shown in chromaffin cells of rodent adrenal medulla, expression of 4.1B was maintained in developed pheochromocytoma, and morphological abnormality or pheochromocytoma generation could not be found in 4.1B-deficient mice. Furthermore, molecular interaction and colocalization of 4.1B and TSLC1 were observed in mouse adrenal gland, but the immunolocalization of TSLC1 along chromaffin cell membranes was not affected in the 4.1B-deficient mice. These results suggest that the function of 4.1B as tumor suppressor might significantly differ among organs and species, and that plasmalemmal retention of TSLC1 would be maintained by molecules other than 4.1B interacting in rodent chromaffin cells.

摘要

蛋白质4.1B是一种在多种器官中表达的膜骨架蛋白,在体外与肺癌-1肿瘤抑制因子(TSLC1)相关。尽管有人提出4.1B参与细胞间连接和肿瘤抑制作用,但一些有争议的结果对4.1B在体内的一般肿瘤抑制功能及其与TSLC1的关系提出了质疑。在本研究中,检测了啮齿动物肾上腺中4.1B的表达及其与TSLC1的相互作用,并使用啮齿动物嗜铬细胞瘤和4.1B基因敲除小鼠研究了4.1B在肿瘤发生中的作用以及4.1B缺乏对TSLC1分布的影响。尽管在啮齿动物肾上腺髓质的嗜铬细胞中显示了4.1B的质膜免疫定位,但在已发生的嗜铬细胞瘤中4.1B的表达得以维持,并且在4.1B基因敲除小鼠中未发现形态异常或嗜铬细胞瘤生成。此外,在小鼠肾上腺中观察到了4.1B与TSLC1的分子相互作用和共定位,但在4.1B基因敲除小鼠中,嗜铬细胞膜上TSLC1的免疫定位并未受到影响。这些结果表明,4.1B作为肿瘤抑制因子的功能可能在不同器官和物种之间存在显著差异,并且在啮齿动物嗜铬细胞中,TSLC1的质膜保留可能由4.1B以外的其他分子相互作用来维持。

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