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Updated: Jul 8, 2026

Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
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.
Abstract:
Abstract Few genes are known to be involved in renal cell carcinoma (RCC) development and progression. The cell-specific transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha) is down-regulated in RCC and we have shown that HNF4 alpha inhibits cell proliferation in the embryonic kidney cell line HEK293. To clarify the possible tumor suppressor activity of HNF4 alpha we analyzed the whole human expression profile in HEK293 cells upon HNF4 alpha induction. By comparing induced and uninduced cells, we identified 1411 differentially expressed genes. Using RNA interference, we screened 56 HNF4 alpha-regulated genes for their possible role in mediating inhibition of cell proliferation triggered by HNF4 alpha. We demonstrate that 14 of these regulated genes are able to contribute to the inhibitory effect of HNF4 alpha 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 HNF4 alpha target genes that regulate proliferation in HEK293 cells. Therefore, we postulate that HNF4 alpha orchestrates, at least, these 14 genes to regulate cell proliferation in HEK293 cells and that down-regulation of HNF4 alpha could contribute to the progression of kidney cancer.
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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