51438

MAGEC2

MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.

OBJECTIVE: To investigate the role of MAGE family member C2 in angiogenesis and epithelial-mesenchymal transition of non-small cell lung carcinoma. METHODS: The cancer Genome Atlas data set was analyzed to filter the highly expressed gene melanoma antigen family C2 in non-small cell lung carcinoma. Quantitative reverse transcription-polymerase chain reaction was performed to verify the overexpression of melanoma antigen family C2 in non-small cell lung carcinoma cell lines. Melanoma antigen family C2 complementary DNA and short hairpin RNA (shRNA) were transfected into SK-MES-1 cells to regulate melanoma antigen family C2 expression. Cell Counting Kit-8 assay, flow cytometry, wound healing assay, and Transwell assay were performed to investigate the effect of melanoma antigen family C2 on proliferation, apoptosis, migration, and invasion of SK-MES-1 cell line. Western blot was used to detect the expression of epithelial-mesenchymal transition markers. Enzyme-linked immunosorbent assay was performed to investigate the secretion of vascular endothelial growth factor, and tube formation assay was conducted to explore the effect of melanoma antigen family C2 on angiogenesis ability of the tumor. tumor xenograft on nude mice and immunohistochemical/hematoxylin and eosin staining were also performed to detect the influence of melanoma antigen family C2 on growth and metastasis of non-small cell lung carcinoma cells. RESULTS: Melanoma antigen family C2 was highly expressed in non-small cell lung carcinoma cells; melanoma antigen family C2 promoted the expression of epithelial-mesenchymal transition-related proteins as well as enhance the secretion of vascular endothelial growth factor and promote angiogenesis; melanoma antigen family C2 promoted proliferation, migration, and invasion and suppressed apoptosis of non-small cell lung carcinoma cells. It could also facilitate growth and metastasis of non-small cell lung carcinoma in vivo. CONCLUSION: Melanoma antigen family C2 was a critical factor of angiogenesis and epithelial-mesenchymal transition in non-small cell lung carcinoma.