title: Transcriptional regulation of microsomal prostaglandin E synthase 1 by the proto-oncogene, c-myc, in the pathogenesis of inflammation and cancer.
abstract: Pro-inflammatory molecules play a key role in the progression of various types of cancers highlighting the importance of studying the pathways that regulate the inflammatory cytokine production. To this end, prostaglandins have been reported to correlate with exacerbated cancer phenotypes that may be prevented by using anti-inflammatory drugs in humans. To understand how the prostaglandin E synthase 1 (mPGES1) may be regulated we analyzed its promoter sequence and identified myc-binding sites. Functional validation was performed by mutating the sites that led to attenuated promoter activation of mPGES1. The known c-myc inhibitor (10058-F4) also blocked PGE2activity, indicating the importance of c-Myc in PGE2synthesis. Isocoumarin analogs were able to reduce the expressions of both c-myc as well as mPGES1 and also inhibit the production of PGE2. Based on these data and the well-established role of c-myc in oncogenesis, we have demonstrated an additional role of c-myc in exacerbating cancers via PGE2production, which may provide a therapeutic opportunity to treat these diseases.
authors.affiliation: Bhupat & Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India. Electronic address: meera.ramanan79@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Ramanan
authors.affiliation: Bhupat & Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India.
authors.forename: V S
authors.initials: VS
authors.lastname: Pilli
authors.affiliation: Bhupat & Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India. Electronic address: agk@iitm.ac.in.
authors.forename: G K
authors.initials: GK
authors.lastname: Aradhyam
authors.affiliation: Bhupat & Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India. Electronic address: mukeshd@iitm.ac.in.
authors.forename: M
authors.initials: M
authors.lastname: Doble
mesh_terms: D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000071876:Prostaglandin-E Synthases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases
keywords: Cancer; Inflammation; Prostaglandins; Transcription factor; c-myc; mPGES1