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BikDDA, a mutant of Bik with longer half-life expression protein, can be a novel therapeutic gene for triple-negative breast cancer.
- Source :
- PLoS ONE, Vol 9, Iss 3, p e92172 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Our previous studies showed that BikDD, a constitutively active mutant form of Bik, exhibited powerful antitumor effects in preclinical pancreatic, lung and breast cancer models. Howerver, the antitumor activity of BikDD in triple-negative breast cancer (TNBC) is unknown. Here we show that aberrant expression of p-ERK1/2 was a meaningful molecular phenotype in TNBC patients, and can be an obstacle for treatment because of the converse correlation with Bik. A novel mutant, BikDDA, in which Ser124 was changed to Alanine to block BikDD phosphorylation by p-ERK1/2 prevented subsequent ubiquitin-proteasome degradation. BikDDA showed a prolonged half-life and enhanced pro-apoptotic ability in TNBC cells compared with BikDD. Moreover, aberrant expression of p-ERK1/2 was associated with 5-fluorouracil resistance in breast cancer patients and BikDDA enhanced the therapeutic effects of 5-fluorouracil in vitro.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.817e068951b47648d5c61d1e6df1234
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0092172