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• W2131570311 abstract "Abstract Tumor metastasis is the major cause of morbidity and mortality in patients with breast cancer. It is critical to identify metastasis enabling genes and understand how they are responsible for inducing specific aspects of the metastatic phenotype to allow for improved clinical detection and management. Protein kinase Cε (PKCε), a member of a family of serine/threonine protein kinases, is a transforming oncogene that has been reported to be involved in cell invasion and motility. In this study, we investigated the role of PKCε in breast cancer development and progression. High-density tissue microarray analysis showed that PKCε protein was detected in 73.6% (106 of 144) of primary tumors from invasive ductal breast cancer patients. Increasing PKCε staining intensity was associated with high histologic grade (P = 0.0206), positive Her2/neu receptor status (P = 0.0419), and negative estrogen (P = 0.0026) and progesterone receptor status (P = 0.0008). Kaplan-Meier analyses showed that PKCε was significantly associated with poorer disease-free and overall survival (log-rank, P = 0.0478 and P = 0.0414, respectively). RNA interference of PKCε in MDA-MB231 cells, an aggressive breast cancer cell line with elevated PKCε levels, resulted in a cell phenotype that was significantly less proliferative, invasive, and motile than the parental or the control RNA interference transfectants. Moreover, in vivo tumor growth of small interfering RNA-PKCε MDA-MB231 clones was retarded by a striking 87% (P &lt; 0.05) and incidence of lung metastases was inhibited by 83% (P &lt; 0.02). PKCε-deficient clones were found to have lower RhoC GTPase protein levels and activation. Taken together, these results revealed that PKCε plays a critical and causative role in promoting an aggressive metastatic breast cancer phenotype and as a target for anticancer therapy." @default.
• W2131570311 created "2016-06-24" @default.
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• W2131570311 date "2005-09-15" @default.
• W2131570311 modified "2023-10-17" @default.
• W2131570311 title "Protein Kinase Cε Is a Predictive Biomarker of Aggressive Breast Cancer and a Validated Target for RNA Interference Anticancer Therapy" @default.
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• W2131570311 doi "https://doi.org/10.1158/0008-5472.can-05-0553" @default.
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