title: Transcriptional regulation of adrenomedullin by oncostatin M in human astroglioma cells: implications for tumor invasion and migration.
abstract: Adrenomedullin (ADM), a secretory peptide with multiple functions in physiological to pathological conditions, is upregulated in several human cancers, including brain, breast, colon, prostate, and lung cancer. However, the molecular mechanisms underlying the regulation of ADM expression in cancerous cells are not fully understood. Here, we report that oncostatin M (OSM), a cytokine belonging to the interleukin-6 family, induces ADM expression in astroglioma cells through induction of signal transducer and activator of transcription-3 (STAT-3) phosphorylation, nuclear translocation, and subsequent DNA binding to the ADM promoter. STAT-3 knockdown decreased OSM-mediated expression of ADM, indicating that ADM expression is regulated by STAT-3 in astroglioma cells. Lastly, scratch wound healing assay showed that astroglioma cell migration was significantly enhanced by ADM peptides. These data suggest that aberrant activation of STAT-3, which is observed in malignant brain tumors, may function as one of the key regulators for ADM expression and glioma invasion.
authors.affiliation: 1] Department of Physiology, Global Top5 Research Program, School of Medicine, Ewha Womans University, Seoul, Korea [2] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Seul Ye
authors.initials: SY
authors.lastname: Lim
authors.affiliation: 1] Department of Physiology, Global Top5 Research Program, School of Medicine, Ewha Womans University, Seoul, Korea [2] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: 1] Department of Physiology, Global Top5 Research Program, School of Medicine, Ewha Womans University, Seoul, Korea [2] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
authors.forename: Jungsul
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
authors.forename: Kyungsun
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
authors.affiliation: 1] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea [2] Department of Pharmacology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Ji Ha
authors.initials: JH
authors.lastname: Choi
authors.affiliation: 1] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea [2] Department of Pharmacology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Park
authors.affiliation: 1] Department of Physiology, Global Top5 Research Program, School of Medicine, Ewha Womans University, Seoul, Korea [2] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
mesh_terms: D053607:Adrenomedullin / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D053683:Oncostatin M; D053607:Adrenomedullin