1. Involvement of Cot activity in the proliferation of ALCL lymphoma cells
- Author
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Margarita, Fernández, Rebeca, Manso, Flavia, Bernaldo de Quirós, Flavia, Bernáldez, Pilar, López, Antonio, Martín-Duce, and Susana, Alemany
- Subjects
CD30 ,JUNB ,Cell ,Biophysics ,Ki-1 Antigen ,P70-S6 Kinase 1 ,Biology ,Biochemistry ,Jurkat cells ,Small hairpin RNA ,Jurkat Cells ,Proto-Oncogene Proteins ,hemic and lymphatic diseases ,medicine ,Humans ,Molecular Biology ,Cell Proliferation ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,Cell growth ,TOR Serine-Threonine Kinases ,Cell Biology ,MAP Kinase Kinase Kinases ,medicine.disease ,Molecular biology ,Lymphoma ,medicine.anatomical_structure ,Lymphoma, Large-Cell, Anaplastic ,RNA Interference - Abstract
Anaplastic large-cell lymphoma (ALCL) cells overexpress CD30 on their cell surface, show increased levels of activated Erk1/2 and of JunB; participating JunB in the proliferative capacity of these lymphomas. Here, we show that ALCL lymphoma cells also present high expression levels of the proto-oncogenic Cot (MAP3K8). Using pharmacological drugs as well as the RNA interference technique we show that Cot protein is responsible for the constitutive Erk1/2 activation in the ALCL lymphoma cells, SUDHL-1. Besides, inhibition of Cot activity reduces the number of cell divisions which is achieved, at least in part, by the control that Cot exercises on the activation state of p70 S6K and on the expression levels of JunB. Since Cot represents an alternative mode, independently of RAF, to activate Erk1/2, all these data strongly suggest that molecular targeting of Cot may be a potential new specific strategy for ALCL lymphomas therapy, without the fully disturbance of the Erk1/2 function. © 2011., This work was supported by a grant from the Ministerio de Ciencia e Innovación (SAF 2008-00819) and Mutua Madrileña.
- Published
- 2011
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