title: Induction of human microsomal prostaglandin E synthase 1 by activated oncogene RhoA GTPase in A549 human epithelial cancer cells.
abstract: Oncogenic RhoA GTPase has been investigated as a mediator of pro-inflammatory responses and aggressive carcinogenesis. Among the various targets of RhoA-linked signals, pro-inflammatory prostaglandin E(2) (PGE(2)), a major prostaglandin metabolite, was assessed in epithelial cancer cells. RhoA activation increased PGE(2) levels and gene expression of the rate-limiting PGE(2) producing enzymes, cyclooxygenase-2 and microsomal prostaglandin E synthase 1 (mPGES-1). In particular, human mPGES-1 was induced by RhoA via transcriptional activation in control and interleukin (IL)-1β-activated cancer cells. To address the involvement of potent signaling pathways in RhoA-activated mPGES-1 induction, various signaling inhibitors were screened for their effects on mPGES-1 promoter activity. RhoA activation enhanced basal and IL-1β-mediated phosphorylated nuclear factor-κB and extracellular signal-regulated kinase1/2 proteins, all of which were positively involved in RhoA-induced gene expression of mPGES-1. As one potent down-stream transcription factor of ERK1/2 signals, early growth response gene 1 product also mediated RhoA-induced gene expression of mPGES-1 by enhancing transcriptional activity. Since oncogene-triggered PGE(2) production is a critical modulator of epithelial tumor cells, RhoA-associated mPGES-1 represents a promising chemo-preventive or therapeutic target for epithelial inflammation and its associated cancers.
authors: Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors: Hye Jin
authors: HJ
authors: Choi
authors: Dong-Hyung
authors: DH
authors: Lee
authors: Seong-Hwan
authors: SH
authors: Park
authors: Juil
authors: J
authors: Kim
authors: Kee Hun
authors: KH
authors: Do
authors: Tae Jin
authors: TJ
authors: An
authors: Young Sup
authors: YS
authors: Ahn
authors: Chung Berm
authors: CB
authors: Park
authors: Yuseok
authors: Y
authors: Moon
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000096:biosynthesis; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051766:Early Growth Response Protein 1; D016328:NF-kappa B; C066737:RHOA protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020742:rhoA GTP-Binding Protein; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone