Validation of Bromodomain and Extraterminal proteins as therapeutic targets in neurofibromatosis type 2.

ABSTRACT:

Background

Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disease characterized by development of schwannomas on the VIIIth (vestibular) cranial nerves. Bromodomain and extra-terminal domain (BET) proteins regulate gene transcription and their activity is required in a variety of cancers including malignant peripheral nerve sheath tumors. The use of BET inhibitors as a therapeutic option to treat NF2 schwannomas has not been explored and is the focus of this study.

Methods

A panel of normal and NF2-null Schwann and schwannoma cell lines were used to characterize the impact of the BET inhibitor JQ1 in vitro and in vivo. The mechanism of action was explored by chromatin immunoprecipitation of the BET BRD4, phospho-kinase arrays and immunohistochemistry (IHC) o

SUBMITTER: Doherty J 

PROVIDER: S-EPMC9278623 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature