Mitogen-activated Protein Kinases Activities and c-erbB-2 Expression in Breast Cancer Carcinogenesis and Progression

ABSTRACT

PURPOSE: Increased level mitogen-activated protein kinase (MAPK) and activation of MAPK have been reported in human breast cancers, especially in breast cancers with HER2/neu overexpression. To understand the relationship between the MAPK protein expressions and other clinico-pathological parameters, we examined the status of MAPKs in 20 breast cancers compared to those of paired normals. METHODS: A total of 20 breast cancers and paired normal breast tissues were included in this study. Tissues were obtained at the operation room and stored at -80degrees C. Tissue proteins were extracted and the concentration was determined by Bio-Rad protein assay method. Western blot analysis were performed to determine the level of MAPKs expressions using 100 ug of tissue protein in 8%, 10%, or 12% sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). MAPK assays were carried out by a non-radioactive method developed by Cell Signaling Tech. as recommened by the manufacturer. Clinico-pathological information was provided from the Breast Cancer Registry of Department of Surgery, Yonsei University College of Medicine. RESULTS: The levels of MAPKs were higher in 95% of breast cancers compared to those of paired normals. The levels of ERK1/2 were significantly higher in cancer tissues compared to paired normals but the activated forms were not. The levels of JNK, p38, and MKP1 proteins were significantly increased in the cancer tissue compared to the paired normals. The levels of ERK1/2 and activated ERK1/2 proteins were not different between tumor stages. There were no significant differences of the levels of ERK1/2 and activated ERK1/2 proteins between HER2-negative and HER2- positive cancers. There were significantly higher levels of activated ERK1/2 proteins in ER-positive cancers than those in ER-negative cancers (P<0.05). CONCLUSION: The levels of MAPKs, but not the activated forms, seem to be increased in breast cancer tissues compared to those of paired normals. The levels of activated MAPKs seem to be associated with estrogen receptor expression in cancer tissues.