Identification of a third Protein 4.1 tumor suppressor, Protein 4.1R, in meningioma pathogenesis.
Meningiomas are common central nervous system tumors; however, the mechanisms underlying their pathogenesis are largely undefined. In this report, we demonstrate that a third Protein 4.1 family member, Protein 4.1R, functions as a meningioma tumor suppressor. We observed loss of Protein 4.1R expression in two meningioma cell lines (IOMM-Lee, CH157-MN) by Western blotting as well as in 6 of 15 sporadic meningiomas by immunohistochemistry and fluorescence in situ hybridization. In support of a meningioma tumor suppressor function, Protein 4.1R overexpression resulted in reduced IOMM-Lee and CH157-MN cell proliferation. Similar to the Protein 4.1B and merlin tumor suppressors, Protein 4.1R membrane localization increased significantly under conditions of growth arrest in vitro. Lastly, we show that Protein 4.1R interacted with a subset of merlin/Protein 4.1B interactors including CD44 and betaII-spectrin. Collectively, these results suggest that Protein 4.1R functions as an important tumor suppressor in the molecular pathogenesis of meningioma.
Robb
Victoria A
VA
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Li
Wen
W
Gascard
Philippe
P
Perry
Arie
A
Mohandas
Narla
N
Gutmann
David H
DH
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000378:metabolism; D003598:Cytoskeletal Proteins; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins; D008578:Meninges / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism*; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013049:Spectrin / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D025581:Neurofibromin 2; D009479:Neuropeptides; D011506:Proteins; D025521:Tumor Suppressor Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D013049:Spectrin