title: uPAR peptide antagonist alters regulation of MAP kinases and Bcl-2 family members in favor of apoptosis in MDA-MB-231 cell line.
abstract: Urokinase plasminogen activator receptor (uPAR) and its ligands play a major role in many tumors by mediating extracellular matrix degradation and signaling cascades leading to tumor growth, invasion and metastasis. Recently we introduced uPAR decapeptide antagonist with cytotoxic effect on MDA-MB-231 cell line. In this study we assessed the alteration in uPAR downstream signaling following treatment with the peptide antagonist. In this regard, extracellular-signal-regulated kinase (ERK) and p38 from mitogen-activated protein kinase family and Bcl-2, Bim and Bax from Bcl-2 protein family were investigated. Our data revealed that the peptide caused p38 activation and low ERK activation. On the other hand, the peptide induced down-regulation of Bcl-2 and up-regulation of Bim without Bax modulation. Changes in target protein expression/activation explain the apoptotic property of the peptide and highlight its potential to be used as a therapeutic agent in cancerous cells expressing high levels of uPAR.
authors.affiliation: Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran.
authors.forename: P
authors.initials: P
authors.lastname: Tarighi
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, I.R. Iran.
authors.forename: H
authors.initials: H
authors.lastname: Montazeri
authors.affiliation: Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran ; Biosensor Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, I.R. Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Khorramizadeh
authors.affiliation: Department of Bioinformatics, Institute of Biochemistry and Biophysics, Tehran University, Tehran, I.R. Iran.
authors.forename: A Madadkar
authors.initials: AM
authors.lastname: Sobhani
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, I.R. Iran.
authors.forename: S N
authors.initials: SN
authors.lastname: Ostad
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, I.R. Iran ; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran.
authors.forename: M H
authors.initials: MH
authors.lastname: Ghahremani
keywords: Bcl-2 family; Bim; ERK; Peptide antagonist; uPAR