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Molecular and Cellular Biology, November 2006, p. 8281-8292, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.00941-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Prostaglandin E₂ Induces Fibroblast Growth Factor 9 via EP3-Dependent Protein Kinase C and Elk-1 Signaling^,

Institute of Basic Medical Sciences,¹ Institute of Molecular Medicine,² Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China³

Received 27 May 2006/ Returned for modification 26 June 2006/ Accepted 3 September 2006

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 (PGE₂) induces expression of FGF-9, which promotes endometriotic stromal cell proliferation, through the EP3 receptor-activated protein kinase C (PKC) signaling pathway. Activation of PKC 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, PKC, 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.

Published ahead of print on 18 September 2006.

Supplemental material for this article may be found at http://mcb.asm.org.

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