HNF4 alpha orchestrates a set of 14 genes to down-regulate cell proliferation in kidney cells

Karen Grigo1, Andrea Wirsing, Belén Lucas

  • 1Institut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Universität Duisburg-Essen, D-45122 Essen, Germany.

Biological Chemistry
|January 1, 2008
PubMed

Insights

Hepatocyte nuclear factor 4 alpha (HNF4 alpha) acts as a tumor suppressor by inhibiting cell proliferation in kidney cancer. This study identified 14 genes regulated by HNF4 alpha that contribute to this inhibitory effect.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Renal cell carcinoma (RCC) involves few known genes.
  • Hepatocyte nuclear factor 4 alpha (HNF4 alpha), a cell-specific transcription factor, is downregulated in RCC.
  • HNF4 alpha inhibits cell proliferation in embryonic kidney cells (HEK293).

Purpose of the Study:

  • To investigate the tumor suppressor activity of HNF4 alpha.
  • To identify genes regulated by HNF4 alpha that mediate its effect on cell proliferation.

Main Methods:

  • Analyzed whole human expression profile in HEK293 cells upon HNF4 alpha induction.
  • Compared gene expression between induced and uninduced cells to identify differentially expressed genes.
  • Used RNA interference to screen 56 HNF4 alpha-regulated genes for their role in proliferation inhibition.

Main Results:

  • Identified 1411 differentially expressed genes upon HNF4 alpha induction.
  • Demonstrated that 14 HNF4 alpha-regulated genes contribute to the inhibition of cell proliferation.
  • Confirmed roles for known cancer genes (e.g., CDKN1A, TGFA) and identified novel genes (e.g., SEPP1, THEM2) in this network.

Conclusions:

  • HNF4 alpha orchestrates a network of at least 14 genes to regulate cell proliferation in HEK293 cells.
  • Down-regulation of HNF4 alpha may contribute to kidney cancer progression.
  • HNF4 alpha represents a potential therapeutic target for renal cell carcinoma.

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