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N-亚硝基二甲胺诱导的肝、肾肿瘤的致瘤潜力比较。

Comparison of the tumorigenic potential of liver and kidney tumors induced by N-nitrosodimethylamine.

机构信息

Department of Microbial Biotechnology and Cell Biology, University of Debrecen, Debrecen, Hungary.

出版信息

Histol Histopathol. 2010 Mar;25(3):309-20. doi: 10.14670/HH-25.309.

Abstract

The aim of the study was to determine the tumorigenic potential of two cell lines established from N-nitrosodimethylamine induced rat hepatocarcinoma (HeDe) and mesenchymal renal tumors (NeDe). The basis of the distinction is that human cancers are known to overexpress facilitative GLUT transporters and TGF-beta1 protein. These proteins are linked to the increased metabolic energy consumption indicating uncontrolled growth and proliferation. We have assayed not only the expression of GLUT-1, GLUT-3 and TGF-beta1 proteins, but also the uptake of 2-fluoro-[18F]-2-deoxy-D-glucose (18FDG), a tracer for cancer diagnosis. Western blot analysis and whole body autoradiography were used to measure the 18FDG uptake of tumor cells. Elevated 18FDG uptake was measured in both tumor cell lines. Whole body autoradiography provided evidence that the uptake of 18FDG was lower in the necrotic inner part than in the more vascularized outer parts of primary hepatocarcinoma and mesenchymal renal tumors. GLUT-1 overexpression in hepatocarcinoma tumor, and high levels of GLUT-3 were found in the NeDe cell line and in the mesenchymal renal tumor. TGF-beta-1 was overexpressed in hepatocarcinoma and mesenchymal renal tumors. In vitro and in vivo parameters support the view that the tumorigenic potential of cancer cells cannot be determined by the expression of a single parameter such as the expression of either GLUT-1, GLUT-3 or 18FDG uptake. Besides the tumorigenic potential of the hepatocarcinoma, the high metabolic activity of the renal tumor indicated by its 18FDG uptake, GLUT-3 and TGF-beta1 expression, the mesenchymal renal tumor induced by N-nitroso-dimethylamine is not a benign, but an an aggressive renal carcinoma.

摘要

本研究旨在确定从 N-亚硝二甲胺诱导的大鼠肝癌(HeDe)和间充质肾肿瘤(NeDe)中建立的两个细胞系的致瘤潜力。其区分的基础是,已知人类癌症过度表达易化型 GLUT 转运蛋白和 TGF-β1 蛋白。这些蛋白与增加的代谢能量消耗有关,表明不受控制的生长和增殖。我们不仅检测了 GLUT-1、GLUT-3 和 TGF-β1 蛋白的表达,还检测了 2-氟-[18F]-2-脱氧-D-葡萄糖(18FDG)的摄取,18FDG 是癌症诊断的示踪剂。Western blot 分析和全身放射自显影用于测量肿瘤细胞的 18FDG 摄取。在两种肿瘤细胞系中均测量到升高的 18FDG 摄取。全身放射自显影提供的证据表明,原发性肝癌和间充质肾肿瘤的坏死内部部分的 18FDG 摄取低于更血管化的外部部分。肝癌肿瘤中 GLUT-1 的过表达,以及 NeDe 细胞系和间充质肾肿瘤中 GLUT-3 的高水平。TGF-β1 在肝癌和间充质肾肿瘤中过表达。体外和体内参数支持这样的观点,即癌细胞的致瘤潜力不能仅通过单个参数的表达来确定,如 GLUT-1、GLUT-3 或 18FDG 摄取的表达。除了肝癌的致瘤潜力外,间充质肾肿瘤的高代谢活性,其 18FDG 摄取、GLUT-3 和 TGF-β1 表达表明,N-亚硝二甲胺诱导的间充质肾肿瘤不是良性的,而是侵袭性肾癌。

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