Basal-type breast cancers are among the most aggressive and deadly breast cancer subtypes, displaying a high metastatic ability associated with mesenchymal features. However, the molecular mechanisms underlying the maintenance of mesenchymal phenotypes of basal-type breast cancer cells remain obscure. Here, we report that KRAS is a critical regulator for the maintenance of mesenchymal features in basal-type breast cancer cells. KRAS is preferentially activated in basal-type breast cancer cells as compared with luminal type. By loss and gain of KRAS, we found that KRAS is necessary and sufficient for the maintenance of mesenchymal phenotypes and metastatic ability through SLUG expression. Taken together, this study demonstrates that KRAS is a critical regulator for the metastatic behavior associated with mesenchymal features of breast cancer cells, implicating a novel therapeutic target for basal-type breast cancer.
Animals ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Models, Animal ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Heterografts ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Phenotype ; Proto-Oncogene Proteins/*genetics/metabolism ; *Transcriptional Activation ; ras Proteins/*genetics/metabolism

BACKGROUND: In this report, we present the annual data of the intensive care unit (ICU) module of the Korean Nosocomial Infections Surveillance System (KONIS) from July 2013 through June 2014. METHODS: We performed a prospective surveillance of nosocomial urinary tract infections (UTIs), bloodstream infections (BSIs), and pneumonia (PNEU) in 166 ICUs of 94 hospitals using the KONIS. Nosocomial infection (NI) rate was defined as the number of infections per 1,000 patient-days or device-days. RESULTS: A total of 2,843 NIs were found during the study period: 861 UTIs (846 were urinary catheter-associated), 1,173 BSIs (1,021 were central line-associated), and 809 PNEUs (498 were ventilator-associated). The rate of urinary catheter-associated UTIs was 1.21 per 1,000 device-days (95% confidence interval [CI]=1.13-1.29), and the urinary catheter utilization ratio was 0.84 (95% CI=0.839-0.841). The rate of central line-associated BSIs was 2.33 per 1,000 device-days (95% CI=2.20-2.48), and the utilization ratio was 0.53 (95% CI=0.529-0.531). The rate of ventilatorassociated PNEUs (VAPs) was 1.46 per 1,000 device-days (95% CI=1.34-1.60), and the utilization ratio was 0.41 (95% CI=0.409-0.411). In hospitals with more than 900 beds, although the ventilator utilization ratio was highest, the rate of VAPs was lower than in hospitals with 300-699 or 700-899 beds. CONCLUSION: BSIs were the most commonly reported nosocomial infections. Although device utilization ratios had increased, nosocomial infection rates did not differ significantly from those during the previous period (July 2012 through June 2013).
Cross Infection* ; Intensive Care Units* ; Critical Care* ; Pneumonia ; Prospective Studies ; Urinary Catheters ; Urinary Tract Infections ; Ventilators, Mechanical