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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 389, Issue 2

Issues

HNF4α orchestrates a set of 14 genes to down-regulate cell proliferation in kidney cells

Karen Grigo
  • 1Institut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Universität Duisburg-Essen, D-45122 Essen, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Andrea Wirsing
  • 2Institut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Universität Duisburg-Essen, D-45122 Essen, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Belén Lucas
  • 3Institut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Universität Duisburg-Essen, D-45122 Essen, Germany and Present address: Bayer Schering Pharma AG, TRG Gynecology and Andrology, D-13342 Berlin, Germany.
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/ Ludger Klein-Hitpass
  • 4Institut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Universität Duisburg-Essen, D-45122 Essen, Germany
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  • De Gruyter OnlineGoogle Scholar
/ Gerhart U. Ryffel
  • 5Institut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Universität Duisburg-Essen, D-45122 Essen, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2008-01-28 | DOI: https://doi.org/10.1515/BC.2008.011

Abstract

Few genes are known to be involved in renal cell carcinoma (RCC) development and progression. The cell-specific transcription factor hepatocyte nuclear factor 4α (HNF4α) is down-regulated in RCC and we have shown that HNF4α inhibits cell proliferation in the embryonic kidney cell line HEK293. To clarify the possible tumor suppressor activity of HNF4α we analyzed the whole human expression profile in HEK293 cells upon HNF4α induction. By comparing induced and uninduced cells, we identified 1411 differentially expressed genes. Using RNA interference, we screened 56 HNF4α-regulated genes for their possible role in mediating inhibition of cell proliferation triggered by HNF4α. We demonstrate that 14 of these regulated genes are able to contribute to the inhibitory effect of HNF4α on cell proliferation, including well-known cancer genes, such as CDKN1A (p21), TGFA, MME (NEP) and ADAMTS1. In addition, the genes SEPP1, THEM2, BPHL, DSC2, ANK3, ALDH6A1, EPHX2, NELL2, EFHD1 and PROS1 are also part of the network of HNF4α target genes that regulate proliferation in HEK293 cells. Therefore, we postulate that HNF4α orchestrates, at least, these 14 genes to regulate cell proliferation in HEK293 cells and that down-regulation of HNF4α could contribute to the progression of kidney cancer.

Keywords: esiRNA; HEK293 cells; HNF4α-regulated genes; renal cell carcinoma; RNA interference; transcription factor

About the article

Corresponding author


Received: 2007-08-09

Accepted: 2007-10-07

Published Online: 2008-01-28

Published in Print: 2008-02-01


Citation Information: Biological Chemistry, Volume 389, Issue 2, Pages 179–187, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: https://doi.org/10.1515/BC.2008.011.

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