title: p38MAPK activation and DUSP10 expression in meningiomas.
abstract: The mitogen activated protein kinase (MAPK) p38MAPK has been implicated in regulation of cell proliferation and apoptosis. However, expression, activation and regulation has not been studied in meningiomas, to our knowledge. p38MAPK is regulated, in part, by dual specificity phosphatases (DUSP) that inactivate signaling by dephosphorylation. DUSP10 is also a likely participant in regulating meningioma proliferation. Five fetal and an adult human leptomeninges and 37 meningioma cultures (MC) were evaluated for DUSP10 as well as phosphorylation of its substrates p38MAPK and p44/42MAPK by western blot and DUSP10 expression by polymerase chain reaction. Platelet derived growth factor-BB (PDGF-BB), transforming growth factor B1 (TGFB1) and cerebrospinal fluid effects on DUSP10 and signaling were also studied in vitro. DUSP10 and phospho-p38MAPK and phospho-p44/42MAPK were detected in all six leptomeninges. DUSP10 was detected in 13 of 17 World Health Organization grade I, 11 of 14 grade II and four of six grade III meningiomas. Phospho-p38MAPK was detected in nine of 17 grade I, two of six grade II, and four of six grade III meningiomas. In the majority of meningiomas DUSP10 expression correlated inversely with phosphorylation of p38MAPK. PDGF-BB increased DUSP10 in MC2 and MC4 and weakly in MC3. TGFB1 increased phosphorylation of p38MAPK and caspase 3 activation. Thus p38MAPK and DUSP10 likely participate in the pathogenesis of meningiomas.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14623, USA. Electronic address: mahlon_johnson@urmc.rochester.edu.
authors.forename: Mahlon D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Jay E
authors.initials: JE
authors.lastname: Reeder
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14623, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Connell
mesh_terms: D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism*; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases; C120407:DUSP10 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; D054637:Dual-Specificity Phosphatases
keywords: DUSP10; Leptomeninges; Meningioma; Phosphatases; p38MAPK; p44/42MAPK