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Objective To investigate the expression of calpain small subunit 1 (Capn4) in breast cancer and its clinical significance. Methods The cancer tissues and the paraffin-embeded specimens of the corresponding adjacent normal tissues from 12 patients with breast cancer between May 2015 and July 2015 in Shanghai General Hospital were collected. The expression of Capn4 was detected by using immunohistochemistry. The paraffin-embeded specimens of cancer tissues from 70 breast cancer patients in Shanghai General Hospital between January 2009 and September 2011 were also collected. And the expression of Capn4 was detected. The correlation between Capn4 expression level and TNM stage, pathological grade, molecular markers as well as the prognosis of breast cancer was also analyzed. Results The expression of Capn4 in breast cancer tissues was higher than that in the corresponding adjacent normal tissues. The expression level of Capn4 was correlated with TNM stage (P = 0.002), T stage (P = 0.004), N stage (P = 0.004), M stage (P = 0.025), estrogen receptor (ER) status (χ 2 = 4.787, P = 0.029) and survival status (χ 2 = 5.826, P = 0.016). Kaplan-Meier survival analysis revealed that the median survival time in the higher expression of Capn4 group 90 months was shorter than that in the lower expression of Capn4 group (not reaching the median survival time), and there were statistical differences (χ 2 = 4.351, P = 0.037). Conclusions The expression of Capn4 in breast cancer tissues is upregulated. The expression difference is correlated with TNM stage, pathological grade, ER status and the prognosis of breast cancer, suggesting that it may become a new target and molecular marker for breast cancer treatment.
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Background and purpose:Ethanol has been reported to stimulate progression of breast cancer, yet the underlying mechanism is not fully understood. This study aimed to investigate effects of ethyl alcohol (EtOH) on the calcium-activated neutral protease (CANP)-cyclin E/focal adhesion kinase (FAK) signaling and cell migration in breast cancer cells, as well as the role of epidermal growth factor receptor (EGFR) in the EtOH-stimulated effects, in order to assess the signaling mechanism(s) underlying how EtOH enhances cancer progression.Methods:Human breast cancer cell line MCF-7 was employed as a model system, with MCF-10A mammary epithelial cells as control. In vitro wound healing assay was carried out to evaluate EtOH-induced cell migration. The effects of EtOH or epidermal growth factor on the proteolysis of cyclin E/FAK were detected by Western blot. EGFR inhibitor (EGFR-I) and a speciifc inhibitor for CANP, Calpeptin, were applied to pretreat cultured cells to explore their inlfuences on the cell migration and cyclin E/FAK proteolysis triggered by EtOH.Results:Treatment of model cells with EtOH (0.3%) stimulated significant proteolysis of cyclin E/FAK in a dose-/time-dependent manner and increased migration (+47.30%,P<0.05) in MCF-7 breast cancer cells, but had no signiifcant effect on migration in MCF-10A cells. Pretreatment with Calpeptin (10 μmol/L) signiifcantly reduced EtOH (0.3%)- or EGFR (10 ng/mL)-induced cyclin E/FAK truncation. EGFR-I (3 μmol/L) pro-foundly reduced EtOH-indcued CANP dependent proteolysis of CANP1 and cyclin E/FAK as well as cell migration (-53.00%,P<0.01).Conclusion:EtOH signiifcantly stimulates activation of CANP via EGFR pathway, resulting in proteolysis of cyclin E/FAK and migration in MCF-7 breast cancer cells, suggesting EGFR-CANP signaling to be a potential target for suppression of metastasis in breast cancer.