Identification of a third Protein 4.1 tumor suppressor, Protein 4.1R, in meningioma pathogenesis

Victoria A. Robb, Wen Li, Philippe Gascard, Arie Perry, Narla Mohandas, David H. Gutmann

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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 βII-spectrin. Collectively, these results suggest that Protein 4.1R functions as an important tumor suppressor in the molecular pathogenesis of meningioma.

Original languageEnglish
Pages (from-to)191-202
Number of pages12
JournalNeurobiology of Disease
Volume13
Issue number3
DOIs
StatePublished - Aug 2003

Keywords

  • Brain tumor
  • CD44
  • Meningioma
  • Merlin
  • Protein 4.1B/DAL-1
  • Protein 4.1R
  • Schwannomin
  • Tumor suppressor

Fingerprint

Dive into the research topics of 'Identification of a third Protein 4.1 tumor suppressor, Protein 4.1R, in meningioma pathogenesis'. Together they form a unique fingerprint.

Cite this