BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma.

ABSTRACT: The bromodomain and extraterminal (BET) domain family of proteins binds to acetylated lysines on histones and regulates gene transcription. Recently, BET inhibitors (BETi) have been developed that show promise as potent anticancer drugs against various solid and hematological malignancies. Here we show that the structurally novel and orally bioavailable BET inhibitor RVX2135 inhibits proliferation and induces apoptosis of lymphoma cells arising in Myc-transgenic mice in vitro and in vivo. We find that BET inhibition exhibits broad transcriptional effects in Myc-transgenic lymphoma cells affecting many transcription factor networks. By examining the genes induced by BETi, which have largely been ignored to date, we discovered that these were similar to those induced by histone deacetylase i

SUBMITTER: Bhadury J 

PROVIDER: S-EPMC4084424 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature