title: Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.
authors: Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.|Sultan Qaboos University, College of Medicine and Health Sciences, Muscat, Oman.
authors: Amira
authors: A
authors: Alkharusi
authors: School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
authors: Shengze
authors: S
authors: Yu
authors: Department of Medicine, Exp Cardiovascular Research Unit and Department of Neurology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Natalia
authors: N
authors: Landázuri
authors: Sultan Qaboos University, College of Medicine and Health Sciences, Muscat, Oman.
authors: Fahad
authors: F
authors: Zadjali
authors: Department of Medicine, Exp Cardiovascular Research Unit and Department of Neurology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Belghis
authors: B
authors: Davodi
authors: Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
authors: Thomas
authors: T
authors: Nyström
authors: School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
authors: Torbjörn
authors: T
authors: Gräslund
authors: Department of Medicine, Exp Cardiovascular Research Unit and Department of Neurology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Afsar
authors: A
authors: Rahbar
authors: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors: Gunnar
authors: G
authors: Norstedt
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D011981:Receptors, Prolactin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006727:Hormone Antagonists; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D011388:Prolactin
keywords: GBM; STAT5; prolactin; prolactin receptor; prolactin receptor antagonist