Original Article

The FOXF2 pathway in the human prostate stroma

  1. Leonie van der Heul-Nieuwenhuijsen1,
  2. Natasja Dits1,
  3. Wilfred Van IJcken2,
  4. Don de Lange1,
  5. Guido Jenster1,*

Article first published online: 26 JUN 2009

DOI: 10.1002/pros.20996

Issue

The Prostate

The Prostate

Volume 69, Issue 14, pages 1538–1547, 1 October 2009

Additional Information

How to Cite

van der Heul-Nieuwenhuijsen, L., Dits, N., Van IJcken, W., de Lange, D. and Jenster, G. (2009), The FOXF2 pathway in the human prostate stroma. The Prostate, 69: 1538–1547. doi: 10.1002/pros.20996

Author Information

  1. 1

    Department of Urology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

  2. 2

    Center for Biomics, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

*Department of Urology, Josephine Nefkens Institute, Erasmus MC, room Be362a, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.

Publication History

  1. Issue published online: 24 AUG 2009
  2. Article first published online: 26 JUN 2009
  3. Manuscript Accepted: 13 MAY 2009
  4. Manuscript Received: 30 DEC 2008

Funded by

  • Netherlands Organization for Scientific Research (ZonMw). Grant Number: 908-02-032

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Keywords:

  • forkhead transcription factors;
  • FOXF2;
  • prostate zones;
  • prostate cancer;
  • extracellular matrix;
  • ECM;
  • epithelial to mesenchymal transition;
  • EMT

Abstract

BACKGROUND

Forkhead box 2 (FOXF2) is a member of the large family of forkhead transcription factors and its expression pattern suggests a role in prostate cancer development. FOXF2 expression is stroma-specific and higher expressed in the prostate transition zone than the prostate peripheral zone. Moreover, expression of FOXF2 is decreased in prostate cancer.

METHODS

To identify the genes and pathways regulated by FOXF2, we compared microarray expression profiles of primary prostate stromal cells (PrSC) treated with control or small interfering RNA (siRNA) directed against FOXF2.

RESULTS

From our microarray analyses, we selected 190 differentially expressed genes, of which 104 genes were higher expressed in PrSC cells treated with FOXF2 siRNA and 86 were higher expressed in PrSC cells treated with negative control siRNA. Eight of the strongest differentially expressed genes were validated by RT-PCR. Genes down-regulated by FOXF2 included MT1E, MT1F, PDGFA, ITGB1, and PSG7 and genes up-regulated by FOXF2 included WASF2, BAMBI, and CXCL12. Ingenuity pathway analysis showed several pathways significantly regulated by FOXF2, including PPAR signaling, PDGF signaling, and extracellular matrix (ECM) signaling. GSEA analysis revealed that FOXF2 up-regulated genes were down-regulated in the same PrSC cells treated with transforming growth factor 3 (TGFβ3).

CONCLUSIONS

The distinct expression pattern of FOXF2 in the prostate, its effect on expression of ECM signaling, and its opposing role in the TGFβ3 pathway, suggests a role for FOXF2 in prostate homeostasis and stroma–epithelial interactions. Prostate 69: 1538–1547, 2009. © 2009 Wiley-Liss, Inc.

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