title: Activation of the pro-migratory bone morphogenetic protein receptor 1B gene in human MDA-MB-468 triple-negative breast cancer cells that over-express CYP2J2.
abstract: Secondary metastases are the leading cause of mortality in patients with breast cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis and metastasis, but at present there is little information on the genes that mediate these actions. In this study MDA-MB-468 breast cancer cells were stably transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was undertaken. We identified 182 genes that were differentially expressed in MDA-2J2 cells relative to control (MDA-CTL) cells (log[fold of control] ≥2). From gene ontology pathway analysis bone morphogenetic protein (BMP) receptor 1B (BMPR1B) emerged as an important upregulated gene in MDA-2J2 cells. Addition of the BMPR1B ligand BMP2 stimulated the migration of MDA-2J2 cells, but not MDA-CTL cells, from 3D-matrigel droplets. Migration of MDA-2J2 cells was prevented by the BMPR antagonist dorsomorphin. These findings indicate that over-expression of CYP2J2 in MDA-MB-468-derived breast cancer cells activates BMPR1B expression that may contribute to increased migration. Targeting BMPR1B may be a novel approach to inhibit the metastatic activity of breast cancers that contain high levels of CYP2J2.
authors.affiliation: Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Allison
authors.affiliation: School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, NSW 2006, Australia.
authors.forename: Yongjuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia.
authors.forename: Nenad
authors.initials: N
authors.lastname: Petrovic
authors.affiliation: Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zimmermann
authors.affiliation: Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Moosmann
authors.affiliation: Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Mirko
authors.initials: M
authors.lastname: Jansch
authors.affiliation: Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Pei H
authors.initials: PH
authors.lastname: Cui
authors.affiliation: School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, NSW 2006, Australia.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dunstan
authors.affiliation: Clinical Pharmacology, Flinders University of South Australia, Bedford Park, SA 5042, Australia.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Mackenzie
authors.affiliation: Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia. Electronic address: michael.murray@sydney.edu.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Murray
mesh_terms: D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015870:Gene Expression; D063990:Gene Ontology; D006801:Humans; D009362:Neoplasm Metastasis; D015533:Transcriptional Activation; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C000717350:CYP2J2 protein, human; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: Bone morphogenetic protein receptor 1B; Breast cancer; Cell migration; Cytochrome P450 2J2; Epoxyfatty acid; Fatty acid biotransformation