HIGH EXPRESSION OF MIEN1 IN BREAST CANCER CORRELATES WITH POOR SURVIVAL OUTCOME

PURPOSE: Breast cancer is the second leading cause of cancer-related deaths in women. Metastasis accounts for majority of breast cancer deaths. It remains a major barrier to cancer treatment due to limitations in diagnosis and lack of effective therapy. Understanding the role of underlying molecular mechanisms involved in metastasis could lead to effective therapy to prevent and treat breast cancer. Migration and Invasion Enhancer 1 (MIEN1), is a novel gene abundantly expressed in different tumors compared to normal cells. Our previous studies have shown it plays a critical role in regulating cell migration and invasion to promote metastases. It is located on chromosome 17q12 near the Her 2/neu oncogene. MIEN1 protein is a membrane-anchored signal protein, with important structural motifs such as the Immunoreceptor tyrosine-based activation motif (ITAM), a redox active motif and a prenylation sequence at the carboxyl terminal. Here, we evaluated the expression of MIEN1 in breast cancer patients with clinical outcome. METHODS: We analyzed The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) database to observe MIEN1 mRNA expression in breast cancer subtypes and its correlation with survival. Also, we assessed MIEN1 expression in a panel of normal and breast cancer cell lines using Western blot. RESULTS: MIEN1 gene expression was significantly increased in different subtypes of breast carcinomas (Invasive ductal carcinoma, Invasive lobular carcinoma, Mixed Ductal and Lobular, and Mucinous) compared to normal tissues. Moreover, MIEN1 is predominantly overexpressed in HER2+ breast cancer patients compared to other subtypes. However, MIEN1 expression in luminal A, luminal B and basal-like subtypes were also high in comparison to normal breast tissues. High expression levels of MIEN1 was associated with reduced overall survival (HR = 1.61; 95% CI = 1.34-1.94, P = 0.0001). Screening of MIEN1 expression in various breast cancer cell lines suggest that expression of MIEN1 is high in majority of them compared to immortalized normal mammary epithelial cell line. CONCLUSION: Our findings confirm that MIEN1 is an important oncogene, and its increased expression in breast cancer contributes towards an aggressive disease with poor survival.