The FOXF2 Pathway in the Human Prostate Stroma

Leonie Nieuwenhuijsen, Natasja Dits, Wilfred van Ijcken, Don Lange, Guido Jenster

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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 (TGF beta 3). CONCLUSIONS. The distinct expression pattern of FOXF2 in the prostate, its effect on expression of ECM signaling, and its opposing role in the TGF beta 3 pathway, suggests a role for FOXF2 in prostate homeostasis and stroma-epithelial interactions. Prostate 69: 1538-1547, 2009. (C) 2009 Wiley-Liss, Inc.
Original languageUndefined/Unknown
Pages (from-to)1538-1547
Number of pages10
JournalProstate
Volume69
Issue number14
Publication statusPublished - 2009

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