Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome.
BACKGROUND
To investigate the expression of EPLIN-alpha, epithelial protein lost in neoplasm, in human breast cancer tissues/cells and investigate the cellular impact of EPLIN-alpha on breast cancer cells.


METHODS
EPLIN-alpha 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-alpha 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-alpha was seen in tumour tissues. Grade-2/3 tumours had significantly lower levels of EPLIN-alpha 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-alpha compared with those with good prognosis (p = 0.0081). Patients who developed recurrence and died of breast cancer had significantly lower levels of EPLIN-alpha 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-alpha transcript had a longer survival than those with low levels. Over-expression of EPLIN-alpha 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.


CONCLUSIONS
It is concluded that expression of EPLIN-alpha in breast cancer is down-regulated in breast cancer cells and tissues, a change linked to the prognosis. EPLIN-alpha acts as a potential tumour suppressor by inhibition of growth and migration of cancer cells.
Jiang
Wen G
WG
Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. jiangw@cf.ac.uk
Martin
Tracey A
TA
Lewis-Russell
Jonathan M
JM
Douglas-Jones
Anthony
A
Ye
Lin
L
Mansel
Robert E
RE
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness
D003598:Cytoskeletal Proteins; C403263:LIMA1 protein, human
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