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HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma

Item Type:Article
Title:HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma
Creators Name:Lucas, B. and Grigo, K. and Erdmann, S. and Lausen, J. and Klein-Hitpass, L. and Ryffel, G.U.
Abstract:Hepatocyte nuclear factor 4{alpha} (HNF4{alpha}) is a tissue-specific transcription factor known to regulate a large number of genes in hepatocytes and pancreatic {beta} cells. Although HNF4{alpha} is highly expressed in some sections of the kidney, little is known about its role in this organ and about HNF4{alpha}-regulated genes in the kidney cells. The abundance and activity of HNF4α are frequently reduced in renal cell carcinoma (RCC) indicating some tumor suppressing function of HNF4{alpha} in renal cells. To determine the potential role of HNF4{alpha} in RCC, we used Flp recombinase-mediated gene integration to generate human embryonic kidney cells (HEK293) that conditionally express wild-type or mutated HNF4α. Expression of wild-type HNF4{alpha} but not of the mutants led to reduction of proliferation and alterations of cell morphology. These effects were reversible and induced at physiological concentrations of HNF4{alpha}. Using gene expression profiling by microarrays, we determined genes regulated by HNF4{alpha}. Interestingly, many of the genes regulated by HNF4{alpha} have been shown to be deregulated in RCC microarray studies. These genes (ACY1, WT1, SELENBP1, COBL, EFHD1, AGXT2L1, ALDH5A1, THEM2, ABCB1, FLJ14146, CSPG2, TRIM9 and HEY1) are good candidates for genes whose activity is changed upon the decrease of HNF4α in RCC.
Keywords:HNF4{alpha}, Microarray, Proliferation, Renal cell carcinoma
Publisher:Nature Publishing Group
Page Range:6418-6431
Date:22 September 2005
Official Publication:https://doi.org/10.1038/sj.onc.1208794
PubMed:View item in PubMed

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