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

Abstract

The aim of the study was to determine thetumorigenic potential of two cell lines established fromN-nitrosodimethylamine induced rat hepatocarcinoma(HeDe) and mesenchymal renal tumors (NeDe). Thebasis of the distinction is that human cancers are knownto overexpress facilitative GLUT transporters and TGF-ß1 protein. These proteins are linked to the increasedmetabolic energy consumption indicating uncontrolledgrowth and proliferation. We have assayed not only theexpression of GLUT-1, GLUT-3 and TGF-ß1 proteins,but also the uptake of 2-fluoro-[18F]-2-deoxi-D-glucose(18FDG), a tracer for cancer diagnosis. Western blotanalysis and whole body autoradiography were used tomeasure the 18FDG uptake of tumor cells. Elevated18FDG uptake was measured in both tumor cell lines.Whole body autoradiography provided evidence that theuptake of 18FDG was lower in the necrotic inner partthan in the more vascularized outer parts of primaryhepatocarcinoma and mesenchymal renal tumors.GLUT-1 overexpression in hepatocarcinoma tumor, andhigh levels of GLUT-3 were found in the NeDe cell lineand in the mesenchymal renal tumor. TGF-ß-1 wasoverexpressed in hepatocarcinoma and mesenchymalrenal tumors. In vitroand in vivo parameters support theview that the tumorigenic potential of cancer cellscannot be determined by the expression of a singleparameter such as the expression of either GLUT-1,GLUT-3 or 18FDG uptake. Besides the tumorigenicpotential of the hepatocarcinoma, the high metabolicactivity of the renal tumor indicated by its 18FDGuptake, GLUT-3 and TGF-ß1 expression, themesenchymal renal tumor induced by N-nitroso-dimethylamine is not a benign, but an an aggressiverenal carcinoma.