Prostaglandin E2 induces fibroblast growth factor 9 via EPS-dependent protein kinase Cδ and Elk-1 signaling

Pei Chin Chuang, H. Sunny Sun, Tsung Ming Chen, Shaw Jenq Tsai

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Fibroblast growth factor 9 (FGF-9) is a potent mitogen that controls the proper development of many tissues and organs. In contrast, aberrant expression of FGF-9 also results in the evolution of many human diseases, such as cancers and endometriosis. Despite its vital function being reported, the cellular and molecular mechanisms responsible for the regulation of FGF-9 expression are mostly unknown. We report here that prostaglandin E2 (PGE 2) induces expression of FGF-9, which promotes endometriotic stromal cell proliferation, through the EP3 receptor-activated protein kinase Cδ (PKCδ) signaling pathway. Activation of PKCδ leads to phosphorylation of ERK1/2, and the transcription factor Elk-1 thereby promotes transcription of FGF-9. Two Elk-1 cis-binding sites located at nucleotides -1324 to -1329 and -1046 to -1051 of the human FGF-9 promoter are identified as crucial for mediating PGE2 actions. Collectively, we demonstrate, for the first time, that PGE2 can directly induce FGF-9 expression via a novel signaling pathway involving EP3, PKCδ, and a member of the ETS domain-containing transcription factor superfamily in primary human endometriotic stromal cells. Our findings may also provide a molecular framework for considering roles for PGE2 in FGF-9-related embryonic development and/or human diseases.

Original languageEnglish
Pages (from-to)8281-8292
Number of pages12
JournalMolecular and Cellular Biology
Volume26
Issue number22
DOIs
Publication statusPublished - 2006 Nov

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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