Unique and selective expression of L-amino acid transporter 1 in human tissue as well as being an aspect of oncofetal protein

Unique and selective expression of L-amino acid transporter 1 in human tissue as well as being an aspect of oncofetal protein
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DOI:
10.14670/hh-29.217
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发表时间:
2014-02-01
影响因子:
2
通讯作者:
Okayasu, Isao
Okayasu, Isao
中科院分区:
生物学4区
文献类型:
--
作者:
Nakada, Norihiro;Mikami, Tetuo;Okayasu, Isao

文献摘要

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L型氨基酸转运蛋白1(LAT 1)的表达失调是多种人类癌症的特征,并可能为化疗提供分子靶点。相反,LAT 2在肿瘤中显示较低的表达。LAT 1被认为是许多癌症的生物标志物,提示是一种癌蛋白。然而,在系统性正常组织中没有进行LAT 1和LAT 2表达的精确分析。为了了解LAT 1和LAT 2的特征,本研究对来自3名成人、3名儿童和3名胎儿的正常人体系统器官和组织中的LAT 1和LAT 2的免疫组织化学表达进行了评估和比较。在胎儿心肌、肝细胞、胸腺上皮细胞和原始神经外胚层细胞中均呈阳性表达,而在相应的成人组织中未发现表达,表明了癌胚蛋白的一个方面。在成人组织中,通过LAT 1和Ki-67的双重免疫染色,发现LAT 1表达于胃肠道粘膜增殖区的近端。睾丸支持细胞、卵巢滤泡细胞和胰岛细胞呈强表达。虽然全身毛细血管内皮细胞不表达LAT 1,但表达LAT 2,对应于血脑,血滤泡和血视网膜屏障的毛细血管表现出强烈的LAT 1免疫反应。总之,LAT 1在性腺组织和几种具有特殊功能的细胞中表达,并被发现是癌胚蛋白的一个方面。此外,普遍存在的LAT 2表达在全身组织中被免疫化学证实,表明宪法功能。
Dysregulated expression of L-type amino acid transporter 1 (LAT1), which transports large neutral amino acids, is a characteristic of various human cancers and possibly offers a molecular target for chemotherapy. LAT2, in contrast, shows lower expression in neoplasms. LAT1 is presumed to be a biomarker of many cancers, suggesting a kind of oncoprotein. However, no precise analysis of LAT1 and LAT2 expression has been performed in systemic normal tissues. To see characteristics of LAT1 and LAT2, immunohistochemical expression of LAT1 and LAT2 was assessed and compared in normal human systemic organs and tissues from 3 adults, 3 children and 3 fetuses in the present study. Cardiac muscles, hepatocytes, thymic epithelial cells and primitive neuroectodermal cells in fetus were positive with LAT1, whereas no expression was found in the respective adult tissues, indicating an aspect of oncofetal protein. In adult tissues, LAT1 was found to be expressed proximal to proliferative zones in gastrointestinal mucosa by double immunostaining of LAT1 and Ki-67. Testicular Sertoli cells, ovarian follicular cells, and pancreatic islet cells showed strong expression. Although the systemic capillary endothelium did not express LAT1, but did express LAT2, capillaries corresponding to the blood-brain, blood-follicle, and blood-retinal barriers demonstrated strong LAT1 immunoreactions. In conclusion, LAT1 was expressed in gonad tissues and several kinds of cells having special functions, as well as being discovered to be an aspect of oncofetal protein. In addition, ubiquitous LAT2 expression was confirmed immunohistochemically in systemic tissues, indicating constitutional function.