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Cells ; 10(4)2021 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-33921698

RESUMEN

MRCKα is a ubiquitously expressed serine/threonine kinase involved in cell contraction and F-actin turnover, which is highly amplified in human breast cancer and part of a gene expression signature for bad prognosis. Nothing is known about the in vivo function of MRCKα. To explore MRCKα function in development and in breast cancer, we generated mice lacking a functional MRCKα gene. Mice were born close to the Mendelian ratio and showed no obvious phenotype including a normal mammary gland formation. Assessing breast cancer development using the transgenic MMTV-PyMT mouse model, loss of MRCKα did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCKα and its related family member MRCKß in two triple-negative breast cancer cell lines resulted in reduced invasion of MDA-MB-231 cells, but did not affect migration of 4T1 cells. Further genomic analysis of human breast cancers revealed that MRCKα is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCKα expression. Collectively, these data suggest that MRCKα might be a prognostic marker for breast cancer, but probably of limited functional importance.


Asunto(s)
Antígenos Transformadores de Poliomavirus/metabolismo , Carcinogénesis/patología , Neoplasias Mamarias Animales/metabolismo , Virus del Tumor Mamario del Ratón/fisiología , Proteína Quinasa de Distrofia Miotónica/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Factores Despolimerizantes de la Actina/metabolismo , Actinas/metabolismo , Animales , Antígenos de Neoplasias/metabolismo , Secuencia de Bases , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Colágeno/farmacología , Modelos Animales de Enfermedad , Femenino , Geles/farmacología , Humanos , Glándulas Mamarias Animales/patología , Neoplasias Mamarias Animales/genética , Virus del Tumor Mamario del Ratón/efectos de los fármacos , Ratones , Ratones Noqueados , Mutación/genética , Miosinas/metabolismo , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas de Neoplasias/metabolismo , Fenotipo , Fosforilación/efectos de los fármacos , Polimerizacion/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Mama Triple Negativas/patología
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