Mrck Alpha Is Dispensable For Breast Cancer Development In The Mmtv-Pymt Model

MRCK alpha 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 MRCK alpha. To explore MRCK alpha function in development and in breast cancer, we generated mice lacking a functional MRCK alpha 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 MRCK alpha did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCK alpha and its related family member MRCK beta 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 MRCK alpha is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCK alpha expression. Collectively, these data suggest that MRCK alpha might be a prognostic marker for breast cancer, but probably of limited functional importance.