Proteomic Identification of 14-3-3e as a Linker Protein between pERK1/2 Inhibition and BIM Upregulation in Human Osteosarcoma Cells
- Authors
- Kim, Kyung Ok; Hsu, Anny C.; Lee, Heon Goo; Patel, Neel; Chandhanayingyong, Chandhanarat; Hickernell, Thomas; Lee, Francis Young-In
- Issue Date
- Jun-2014
- Publisher
- WILEY
- Keywords
- pERK1; 2; Bim; 14-3-3E; pro-apoptotic effect; osteosarcoma cells
- Citation
- JOURNAL OF ORTHOPAEDIC RESEARCH, v.32, no.6, pp.848 - 854
- Journal Title
- JOURNAL OF ORTHOPAEDIC RESEARCH
- Volume
- 32
- Number
- 6
- Start Page
- 848
- End Page
- 854
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12585
- DOI
- 10.1002/jor.22598
- ISSN
- 0736-0266
- Abstract
- Despite advancements in multimodality chemotherapy, conventional cytotoxic treatments still remain ineffective for a subset of patients with aggressive metastatic or multifocal osteosarcoma. It has been shown that pERK1/2 inhibition enhances chemosensitivity to doxorubicin and promotes osteosarcoma cell death in vivo and in vitro. One of the pro-apoptotic mechanisms is upregulation of Bim by pERK1/2 inhibitors. To this end, we examined proteomic changes of 143B human osteosarcoma cells with and without treatment of PD98059, pERK1/2 inhibitor. Specifically, we identified 14-3-3E protein as a potential mediator of Bim expression in response to inhibition of pERK1/2. We hypothesized that 14-3-3E mediates upregulation of Bim expression after pERK1/2 inhibition. We examined the expression of Bim after silencing 14-3-3E using siRNA. The 14-3-3E gene silencing resulted in downregulation of Bim expression after PD98059 treatment. These data indicate that 14-3-3E is required for Bim expression and that it has an anti-cancer effect under pERK1/2 inhibition in 143B cells. By playing an essential role upstream of Bim, 14-3-3E may potentially be a coadjuvant factor synergizing the effect of pERK1/2 inhibitors in addition to conventional cytotoxic agents for more effective osteosarcoma treatments. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:848-854, 2014.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - ETC > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12585)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.