Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2

Benjamin M. Wahle, Eric T. Hawley, Yongzheng He, Abbi E. Smith, Jin Yuan, Andi R. Masters, David R. Jones, Jeffrey R. Gehlhausen, Su Jung Park, Simon Conway, D. Clapp, Charles Yates

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Mutations in the tumor suppressor gene NF2 lead to Neurofibromatosis type 2 (NF2), a tumor predisposition syndrome characterized by the development of schwannomas, including bilateral vestibular schwannomas with complete penetrance. Recent work has implicated the importance of COX-2 in schwannoma growth. Using a genetically engineered murine model of NF2, we demonstrate that selective inhibition of COX-2 with celecoxib fails to prevent the spontaneous development of schwannomas or sensorineural hearing loss in vivo, despite elevated expression levels of COX-2 in Nf2-deficient tumor tissue. These results suggest that COX-2 is nonessential to schwannomagenesis and that the proposed tumor suppressive effects of NSAIDs on schwannomas may occur through COX-2 independent mechanisms.

Original languageEnglish (US)
Pages (from-to)718-725
Number of pages8
JournalOncotarget
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Celecoxib
Neurofibromatosis 2
Sensorineural Hearing Loss
Neurilemmoma
Neoplasms
Acoustic Neuroma
Penetrance
Non-Steroidal Anti-Inflammatory Agents
Tumor Suppressor Genes
Mutation
Growth

Keywords

  • Cyclooxygenase 2
  • Neurofibromatosis type 2
  • Non-steroidal anti-inflammatory agents
  • Transgenic mice
  • Vestibular schwannoma

ASJC Scopus subject areas

  • Oncology

Cite this

Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2. / Wahle, Benjamin M.; Hawley, Eric T.; He, Yongzheng; Smith, Abbi E.; Yuan, Jin; Masters, Andi R.; Jones, David R.; Gehlhausen, Jeffrey R.; Park, Su Jung; Conway, Simon; Clapp, D.; Yates, Charles.

In: Oncotarget, Vol. 9, No. 1, 01.01.2018, p. 718-725.

Research output: Contribution to journalArticle

Wahle, Benjamin M. ; Hawley, Eric T. ; He, Yongzheng ; Smith, Abbi E. ; Yuan, Jin ; Masters, Andi R. ; Jones, David R. ; Gehlhausen, Jeffrey R. ; Park, Su Jung ; Conway, Simon ; Clapp, D. ; Yates, Charles. / Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2. In: Oncotarget. 2018 ; Vol. 9, No. 1. pp. 718-725.
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