Altering Chemosensitivity by Modulating Translation Elongation

• DOI: 10.1371/journal.pone.0005428
• Publication Date: 2009-04-30T22:07:55Z
• Authors: Francis Robert; Marilyn Carrier; Svea Rawe; Samuel Chen; Scott Lowe; Jerry Pelletier
• Keywords: EIF4E

The process of translation occurs at a nexus point downstream number signal pathways and developmental processes. Modeling activation the PTEN/AKT/mTOR pathway in Emu-Myc mouse is valuable tool to study tumor genotype/chemosensitivity relationships vivo. In this model, blocking initiation with silvestrol, an inhibitor ribosome recruitment step has been showed modulate sensitivity tumors effect standard chemotherapy. However, inhibitors elongation have tested as potential anti-cancer therapeutic agents vitro, but not extensively genetically well-defined models or for synergy care agents.Here, we chose four structurally different chemical elongation: homoharringtonine, bruceantin, didemnin B cycloheximide, their ability alter chemoresistance Emu-myc lymphomas harbouring lesions Pten, Tsc2, Bcl-2, eIF4E. We show that some genetic settings, are able synergize doxorubicin by reinstating apoptotic program cells. attribute reduction levels pro-oncogenic pro-survival proteins having short half-lives, like Mcl-1, cyclin D1 c-Myc. Using cells grown ex vivo reproduced observed mice between chemotherapy inhibition reversed protein degradation proteasome inhibitor.Our results indicate depleting short-lived factors inhibiting synthesis could achieve response harboring mutations.