Increased expression of MNK1b, the spliced isoform of MNK1, predicts poor prognosis and is associated with triple-negative breast cancer
| Autor: | Eva M. García-Recio, Marta García-Hernández, Lara Sanz-Criado, Noelia Martínez-Jañez, M Val Toledo-Lobo, M. Elena Martín, M. Isabel Pérez-Morgado, Mercedes García-Villanueva, Celia Pinto-Díez, Isabel Esteban-Rodríguez, Belén Pérez-Mies, Víctor M. González, Silvia Sacristán, Alejandro Pascual |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene isoform MNK1 Biology pronostic marker 03 medical and health sciences 0302 clinical medicine Breast cancer breast cancer molecular tumor type medicine Triple-negative breast cancer triple-negative Oncogene Kinase EIF4E medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Mitogen-activated protein kinase biology.protein Cancer research Phosphorylation Research Paper |
| Zdroj: | Oncotarget Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| ISSN: | 1949-2553 |
| Popis: | MAP kinase interacting kinases (MNKs) modulate the function of oncogene eukaryotic initiation factor 4E (eIF4E) through phosphorylation, which is necessary for oncogenic transformation. MNK1 gives rise to two mRNAs and thus two MNK1 isoforms, named MNK1a and MNK1b. MNK1b, the splice variant of human MNK1a, is constitutively active and independent of upstream MAP kinases. In this study, we have analyzed the expression of both MNK1 isoforms in 69 breast tumor samples and its association with clinicopathologic/prognostic characteristics of breast cancer. MNK1a and MNK1b expression was significantly increased in tumors relative to the corresponding adjacent normal tissue (p < 0.001). In addition, MNK1b overexpression was found in most of the triple-negative tumors and was associated with a shorter overall and disease-free survival time. Overexpression of MNK1b in MDA-MB-231 cells induced an increase in the expression of the MCL1 antiapoptotic protein and promoted proliferation, invasion and colony formation. In conclusion, a high expression level of MNK1b protein could be used as a marker of poor prognosis in breast cancer patients and it could be a therapeutic target in triple-negative tumors. |
| Databáze: | OpenAIRE |
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