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

Jiang WG, Martin TA, Lewis-Russell JM, Douglas-Jones A, Ye L, Mansel RE - Mol. Cancer (2008)

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. jiangw@cf.ac.uk

ABSTRACT

Introduction: 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.

Experimental design: 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.

Conclusion: 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.

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ERK inhibitor reversed the action of EPLIN-α , an ECIS based wounding analysis. Wild type, control cells and EPLIN-α expression MDA MB231 cells were tested in the absence or presence of ERK inhibitor. The reduction of migration in MDA MB231 over-expressing EPLIN-α was reverse by ERK inhibitor.
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Figure 5: ERK inhibitor reversed the action of EPLIN-α , an ECIS based wounding analysis. Wild type, control cells and EPLIN-α expression MDA MB231 cells were tested in the absence or presence of ERK inhibitor. The reduction of migration in MDA MB231 over-expressing EPLIN-α was reverse by ERK inhibitor.

Mentions: In searching for the potential pathway(s) that may be responsible for the action of EPLIN-α , we have screened a panel of small molecule inhibitors to some of the key signalling pathways that are linked to cell motility. They included ROCK inhibitor, JAK3 inhibitor, JNK inhibitor, PI3K inhibitor, PKC inhibitor and ERK inhibitor. Only the ERK inhibitor was seen to partially restore the inhibitory effect of EPLIN-α on the motility of the cancer cells as shown in figure 5. ERK inhibitor has only a marginal effect on the motility of the control breast cancer cells, however, it reverse the inhibition of motility in the MDA MB231EPLINexp cells to nearing the control level. This was more obvious at the early phase (within 2 hours after wounding) (figure 5).


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

Jiang WG, Martin TA, Lewis-Russell JM, Douglas-Jones A, Ye L, Mansel RE - Mol. Cancer (2008)

ERK inhibitor reversed the action of EPLIN-α , an ECIS based wounding analysis. Wild type, control cells and EPLIN-α expression MDA MB231 cells were tested in the absence or presence of ERK inhibitor. The reduction of migration in MDA MB231 over-expressing EPLIN-α was reverse by ERK inhibitor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553413&req=5

Figure 5: ERK inhibitor reversed the action of EPLIN-α , an ECIS based wounding analysis. Wild type, control cells and EPLIN-α expression MDA MB231 cells were tested in the absence or presence of ERK inhibitor. The reduction of migration in MDA MB231 over-expressing EPLIN-α was reverse by ERK inhibitor.
Mentions: In searching for the potential pathway(s) that may be responsible for the action of EPLIN-α , we have screened a panel of small molecule inhibitors to some of the key signalling pathways that are linked to cell motility. They included ROCK inhibitor, JAK3 inhibitor, JNK inhibitor, PI3K inhibitor, PKC inhibitor and ERK inhibitor. Only the ERK inhibitor was seen to partially restore the inhibitory effect of EPLIN-α on the motility of the cancer cells as shown in figure 5. ERK inhibitor has only a marginal effect on the motility of the control breast cancer cells, however, it reverse the inhibition of motility in the MDA MB231EPLINexp cells to nearing the control level. This was more obvious at the early phase (within 2 hours after wounding) (figure 5).

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. jiangw@cf.ac.uk

ABSTRACT

Introduction: 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.

Experimental design: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus