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The Truncate Mutation of Notch2 Enhances Cell Proliferation through Activating the NF-κB Signal Pathway in the Diffuse Large B-Cell Lymphomas.
- Source :
- PLoS ONE; Oct2014, Vol. 9 Issue 10, p1-11, 11p
- Publication Year :
- 2014
-
Abstract
- The Notch2 is a critical membrane receptor for B-cell functions, and also displays various biological roles in lymphoma pathogenesis. In this article, we reported that 3 of 69 (4.3%) diffuse large B-cell lymphomas (DLBCLs) exhibited a truncate NOTCH2 mutation at the nucleotide 7605 (G/A) in the cDNA sequence, which led to partial deletion of the C-terminal of PEST (proline-, glutamic acid-, serine- and threonine-rich) domain. The truncate Notch2 activated both the Notch2 and the NF-κB signals and promoted the proliferation of B-cell lymphoma cell lines, including DLBCL and Burkitt's lymphoma cell lines. Moreover, the ectopic proliferation was completely inhibited by ammonium pyrrolidinedithiocarbamate (PDTC), an NF-κB inhibitor. Simultaneously, PDTC also reduced the expression level of Notch2. Based on these results, we conclude that the Notch2 receptor with PEST domain truncation enhances cell proliferation which may be associated with the activation of the Notch2 and the NF-κB signaling. Our results are expected to provide a possible target for new DLBCL therapies by suppressing the Notch2 and the NF-κB signaling. [ABSTRACT FROM AUTHOR]
- Subjects :
- CELL proliferation
B cells
ANTISENSE DNA
NUCLEOTIDES
PYRROLIDINE
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 99199375
- Full Text :
- https://doi.org/10.1371/journal.pone.0108747