Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells
Krysov, Sergey, Dias, S, Paterson, A, Mockridge, C. Ian, Potter, Kathleen N., Smith, Katherine C., Ashton-Key, Margaret, Stevenson, Freda K. and Packham, Graham (2012) Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells. Blood, 119, (1), 170-179. (doi:10.1182/blood-2011-07-370403). (PMID:22086413).
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Although long considered as a disease of failed apoptosis, it is now clear that chronic lymphocytic leukemia (CLL) cells undergo extensive cell division in vivo, especially in progressive disease. Signaling via the B-cell receptor is thought to activate proliferation and survival pathways in CLL cells and also has been linked to poor outcome. Here, we have analyzed the expression of the proto-oncoprotein MYC, an essential positive regulator of the cell cycle, after stimulation of surface IgM (sIgM). MYC expression was rapidly increased after sIgM stimulation in a subset of CLL samples. The ability of sIgM stimulation to increase MYC expression was correlated with sIgM-induced intracellular calcium fluxes. MYC induction was partially dependent on the MEK/ERK signaling pathway, and MYC and phosphorylated ERK1/2 were both expressed within proliferation centers in vivo. Although stimulation of sIgD also resulted in ERK1/2 phosphorylation, responses were relatively short lived compared with sIgM and were associated with significantly reduced MYC induction, suggesting that the kinetics of ERK1/2 activation is a critical determinant of MYC induction. Our results suggest that ERK1/2-dependent induction of MYC is likely to play an important role in antigen-induced CLL cell proliferation.
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)|
|Divisions:||Faculty of Medicine > Cancer Sciences
|Date Deposited:||28 May 2012 14:07|
|Last Modified:||06 Aug 2015 03:06|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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