Prostaglandin F-F-prostanoid receptor regulates CXCL8 expression in endometrial adenocarcinoma cells via the calcium-calcineurin-NFAT pathway

Kurt J. Sales, David Maldonado-Pérez, Vivien Grant, Rob D. Catalano, Martin R. Wilson, Pamela Brown, Alistair R W Williams, Richard A. Anderson, E Aubrey Thompson, Henry N. Jabbour

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Pro-inflammatory mediators, like prostaglandin (PG) and chemokines, promote tumourigenesis by enhancing cell proliferation, migration of immune cells and recruitment of blood vessels. Recently we showed elevated expression of the chemokine (C-X-C motif) receptor 2 (CXCR2) in endometrial adenocarcinomas localized to neutrophils and neoplastic epithelial and vascular cells. Furthermore we found that PGF-F-prostanoid (FP) receptor regulates the expression of the CXCR2 ligand CXCL1, to promote neutrophil chemotaxis in endometrial adenocarcinomas. In the present study we identified another CXCR2 ligand, CXCL8 as a target for PGF-FP receptor signalling which enhances epithelial cell proliferation in endometrial adenocarcinoma cells in vitro and in nude mice in vivo. We found that PGF-FP receptor interaction induces CXCL8 expression in endometrial adenocarcinoma cells via the protein kinase C-calcium-calcineurin-NFAT signaling pathway. Promoter analysis revealed that CXCL8 transcriptional activation by PGF signaling is mediated by cooperative interactions between the AP1 and NFAT binding sites. Furthermore, PGF via the FP receptor induced the expression of the regulator of calcineurin 1 isoform 4 (RCAN1-4) via the calcineurin/NFAT pathway in a reciprocal manner to CXCL8. Using an adenovirus to overexpress RCAN1-4, we found that RCAN1-4 is a negative regulator of CXCL8 expression in endometrial adenocarcinoma cells. Taken together our data have elucidated the molecular and cellular mechanism whereby PGF regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression which may be exploited therapeutically to inhibit CXCL8-mediated tumour development.

Original languageEnglish (US)
Pages (from-to)1917-1928
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1793
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Dinoprost
Calcineurin
Prostaglandins F
Prostaglandins
Adenocarcinoma
Calcium
Protein Isoforms
Blood Vessels
Neutrophils
CCR Receptors
Epithelial Cells
Cell Proliferation
Ligands
Chemotaxis
Chemokines
Adenoviridae
Nude Mice
Protein Kinase C
Transcriptional Activation
Cell Movement

Keywords

  • Calcineurin
  • Chemokine
  • CXCL8
  • FP receptor
  • PGF
  • Prostaglandin

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Prostaglandin F-F-prostanoid receptor regulates CXCL8 expression in endometrial adenocarcinoma cells via the calcium-calcineurin-NFAT pathway. / Sales, Kurt J.; Maldonado-Pérez, David; Grant, Vivien; Catalano, Rob D.; Wilson, Martin R.; Brown, Pamela; Williams, Alistair R W; Anderson, Richard A.; Thompson, E Aubrey; Jabbour, Henry N.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1793, No. 12, 12.2009, p. 1917-1928.

Research output: Contribution to journalArticle

Sales, Kurt J. ; Maldonado-Pérez, David ; Grant, Vivien ; Catalano, Rob D. ; Wilson, Martin R. ; Brown, Pamela ; Williams, Alistair R W ; Anderson, Richard A. ; Thompson, E Aubrey ; Jabbour, Henry N. / Prostaglandin F-F-prostanoid receptor regulates CXCL8 expression in endometrial adenocarcinoma cells via the calcium-calcineurin-NFAT pathway. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2009 ; Vol. 1793, No. 12. pp. 1917-1928.
@article{e27149851ea64fc5b5ced9580c2330f5,
title = "Prostaglandin F2α-F-prostanoid receptor regulates CXCL8 expression in endometrial adenocarcinoma cells via the calcium-calcineurin-NFAT pathway",
abstract = "Pro-inflammatory mediators, like prostaglandin (PG) and chemokines, promote tumourigenesis by enhancing cell proliferation, migration of immune cells and recruitment of blood vessels. Recently we showed elevated expression of the chemokine (C-X-C motif) receptor 2 (CXCR2) in endometrial adenocarcinomas localized to neutrophils and neoplastic epithelial and vascular cells. Furthermore we found that PGF2α-F-prostanoid (FP) receptor regulates the expression of the CXCR2 ligand CXCL1, to promote neutrophil chemotaxis in endometrial adenocarcinomas. In the present study we identified another CXCR2 ligand, CXCL8 as a target for PGF2α-FP receptor signalling which enhances epithelial cell proliferation in endometrial adenocarcinoma cells in vitro and in nude mice in vivo. We found that PGF2α-FP receptor interaction induces CXCL8 expression in endometrial adenocarcinoma cells via the protein kinase C-calcium-calcineurin-NFAT signaling pathway. Promoter analysis revealed that CXCL8 transcriptional activation by PGF2α signaling is mediated by cooperative interactions between the AP1 and NFAT binding sites. Furthermore, PGF2α via the FP receptor induced the expression of the regulator of calcineurin 1 isoform 4 (RCAN1-4) via the calcineurin/NFAT pathway in a reciprocal manner to CXCL8. Using an adenovirus to overexpress RCAN1-4, we found that RCAN1-4 is a negative regulator of CXCL8 expression in endometrial adenocarcinoma cells. Taken together our data have elucidated the molecular and cellular mechanism whereby PGF2α regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression which may be exploited therapeutically to inhibit CXCL8-mediated tumour development.",
keywords = "Calcineurin, Chemokine, CXCL8, FP receptor, PGF, Prostaglandin",
author = "Sales, {Kurt J.} and David Maldonado-P{\'e}rez and Vivien Grant and Catalano, {Rob D.} and Wilson, {Martin R.} and Pamela Brown and Williams, {Alistair R W} and Anderson, {Richard A.} and Thompson, {E Aubrey} and Jabbour, {Henry N.}",
year = "2009",
month = "12",
doi = "10.1016/j.bbamcr.2009.09.018",
language = "English (US)",
volume = "1793",
pages = "1917--1928",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "12",

}

TY - JOUR

T1 - Prostaglandin F2α-F-prostanoid receptor regulates CXCL8 expression in endometrial adenocarcinoma cells via the calcium-calcineurin-NFAT pathway

AU - Sales, Kurt J.

AU - Maldonado-Pérez, David

AU - Grant, Vivien

AU - Catalano, Rob D.

AU - Wilson, Martin R.

AU - Brown, Pamela

AU - Williams, Alistair R W

AU - Anderson, Richard A.

AU - Thompson, E Aubrey

AU - Jabbour, Henry N.

PY - 2009/12

Y1 - 2009/12

N2 - Pro-inflammatory mediators, like prostaglandin (PG) and chemokines, promote tumourigenesis by enhancing cell proliferation, migration of immune cells and recruitment of blood vessels. Recently we showed elevated expression of the chemokine (C-X-C motif) receptor 2 (CXCR2) in endometrial adenocarcinomas localized to neutrophils and neoplastic epithelial and vascular cells. Furthermore we found that PGF2α-F-prostanoid (FP) receptor regulates the expression of the CXCR2 ligand CXCL1, to promote neutrophil chemotaxis in endometrial adenocarcinomas. In the present study we identified another CXCR2 ligand, CXCL8 as a target for PGF2α-FP receptor signalling which enhances epithelial cell proliferation in endometrial adenocarcinoma cells in vitro and in nude mice in vivo. We found that PGF2α-FP receptor interaction induces CXCL8 expression in endometrial adenocarcinoma cells via the protein kinase C-calcium-calcineurin-NFAT signaling pathway. Promoter analysis revealed that CXCL8 transcriptional activation by PGF2α signaling is mediated by cooperative interactions between the AP1 and NFAT binding sites. Furthermore, PGF2α via the FP receptor induced the expression of the regulator of calcineurin 1 isoform 4 (RCAN1-4) via the calcineurin/NFAT pathway in a reciprocal manner to CXCL8. Using an adenovirus to overexpress RCAN1-4, we found that RCAN1-4 is a negative regulator of CXCL8 expression in endometrial adenocarcinoma cells. Taken together our data have elucidated the molecular and cellular mechanism whereby PGF2α regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression which may be exploited therapeutically to inhibit CXCL8-mediated tumour development.

AB - Pro-inflammatory mediators, like prostaglandin (PG) and chemokines, promote tumourigenesis by enhancing cell proliferation, migration of immune cells and recruitment of blood vessels. Recently we showed elevated expression of the chemokine (C-X-C motif) receptor 2 (CXCR2) in endometrial adenocarcinomas localized to neutrophils and neoplastic epithelial and vascular cells. Furthermore we found that PGF2α-F-prostanoid (FP) receptor regulates the expression of the CXCR2 ligand CXCL1, to promote neutrophil chemotaxis in endometrial adenocarcinomas. In the present study we identified another CXCR2 ligand, CXCL8 as a target for PGF2α-FP receptor signalling which enhances epithelial cell proliferation in endometrial adenocarcinoma cells in vitro and in nude mice in vivo. We found that PGF2α-FP receptor interaction induces CXCL8 expression in endometrial adenocarcinoma cells via the protein kinase C-calcium-calcineurin-NFAT signaling pathway. Promoter analysis revealed that CXCL8 transcriptional activation by PGF2α signaling is mediated by cooperative interactions between the AP1 and NFAT binding sites. Furthermore, PGF2α via the FP receptor induced the expression of the regulator of calcineurin 1 isoform 4 (RCAN1-4) via the calcineurin/NFAT pathway in a reciprocal manner to CXCL8. Using an adenovirus to overexpress RCAN1-4, we found that RCAN1-4 is a negative regulator of CXCL8 expression in endometrial adenocarcinoma cells. Taken together our data have elucidated the molecular and cellular mechanism whereby PGF2α regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression which may be exploited therapeutically to inhibit CXCL8-mediated tumour development.

KW - Calcineurin

KW - Chemokine

KW - CXCL8

KW - FP receptor

KW - PGF

KW - Prostaglandin

UR - http://www.scopus.com/inward/record.url?scp=72049130544&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72049130544&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2009.09.018

DO - 10.1016/j.bbamcr.2009.09.018

M3 - Article

VL - 1793

SP - 1917

EP - 1928

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

SN - 0167-4889

IS - 12

ER -