Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome

INTRODUCTION: To investigate the expression of EPLIN-α, epithelial protein lost in neoplasm, in human breast cancer tissues/cells and investigate the cellular impact of EPLIN-α on breast cancer cells. EXPERIMENTAL DESIGN: EPLIN-α was determined in tumour (n = 120) and normal mammary tissues (n = 32), and cancer cell lines (n = 16). Cell invasion, in vitro and in vivo growth of cells transfected with EPLIN-α were evaluated using in vitro invasion assay, in vitro and in vivo tumour model. Cellular migration was analysed using Electric Cell Impedance Sensing assays. RESULTS: Low level of EPLIN-α was seen in tumour tissues. Grade-2/3 tumours had significantly lower levels of EPLIN-α compared with grade-1 (p = 0.047 and p = 0.046 vs grade-1, respectively). Patients with poor prognosis had a significantly lower levels of EPLIN-α compared with those with good prognosis (p = 0.0081). Patients who developed recurrence and died of breast cancer had significantly lower levels of EPLIN-α compared with those who remained disease free (p = 0.0003 and p = 0.0008, respectively) (median follow-up 10 years). Patients with high levels of EPLIN-α transcript had a longer survival than those with low levels. Over-expression of EPLIN-α in breast cancer cells by way of transfection rendered cells less invasive, less motile and growing at a slower pace in vitro and in vivo. An ERK inhibitor was shown to be able to abolish the effect of EPLIN expression. CONCLUSION: It is concluded that expression of EPLIN-α in breast cancer is down-regulated in breast cancer cells and tissues, a change linked to the prognosis. EPLIN-α acts as a potential tumour suppressor by inhibition of growth and migration of cancer cells.