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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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EPLIN-α expression on cell migration as analysed by ECIS. A: wounding assays. Cells were first wounded at 6 v for 30 sec. The impedance change was shown. Electrode – A1: MDA-MB231wt, A2: MDA-MB231pEF/His, A3: MDA-MB231EPLINexp3, A4: MDA-MB231EPLINexp4. The breast cancer cells which over-expressed EPLIN-α showed a markedly reduced migration. B and C: ECIS RbA modelling of cell motility indicated a significant reduction of motility in EPLIN-α transfected cells as shown by resistance in B and capacitance in C. * p < 0.01 vs MDA-MB231wt and MDA-MB231pEF/His.
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Figure 4: EPLIN-α expression on cell migration as analysed by ECIS. A: wounding assays. Cells were first wounded at 6 v for 30 sec. The impedance change was shown. Electrode – A1: MDA-MB231wt, A2: MDA-MB231pEF/His, A3: MDA-MB231EPLINexp3, A4: MDA-MB231EPLINexp4. The breast cancer cells which over-expressed EPLIN-α showed a markedly reduced migration. B and C: ECIS RbA modelling of cell motility indicated a significant reduction of motility in EPLIN-α transfected cells as shown by resistance in B and capacitance in C. * p < 0.01 vs MDA-MB231wt and MDA-MB231pEF/His.

Mentions: Here, we adopted the Electric Cell Impedance Sensing (ECIS) method to investigate the impact of EPLIN-α over-expression on cell motility. As shown in Figure 4A, EPLIN-α over-expressing breast cancer cells showed a dramatic slowdown in recovery after electric wounding. Using ECIS-RbA modelling system, it was shown that EPLIN-α over-expression in the MDAMB231EPLINexp cells resulted in a significant reduction in both resistance and capacitance, when compared with both the wild type cells and the control cells (figure 4B and 4C).


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)

EPLIN-α expression on cell migration as analysed by ECIS. A: wounding assays. Cells were first wounded at 6 v for 30 sec. The impedance change was shown. Electrode – A1: MDA-MB231wt, A2: MDA-MB231pEF/His, A3: MDA-MB231EPLINexp3, A4: MDA-MB231EPLINexp4. The breast cancer cells which over-expressed EPLIN-α showed a markedly reduced migration. B and C: ECIS RbA modelling of cell motility indicated a significant reduction of motility in EPLIN-α transfected cells as shown by resistance in B and capacitance in C. * p < 0.01 vs MDA-MB231wt and MDA-MB231pEF/His.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: EPLIN-α expression on cell migration as analysed by ECIS. A: wounding assays. Cells were first wounded at 6 v for 30 sec. The impedance change was shown. Electrode – A1: MDA-MB231wt, A2: MDA-MB231pEF/His, A3: MDA-MB231EPLINexp3, A4: MDA-MB231EPLINexp4. The breast cancer cells which over-expressed EPLIN-α showed a markedly reduced migration. B and C: ECIS RbA modelling of cell motility indicated a significant reduction of motility in EPLIN-α transfected cells as shown by resistance in B and capacitance in C. * p < 0.01 vs MDA-MB231wt and MDA-MB231pEF/His.
Mentions: Here, we adopted the Electric Cell Impedance Sensing (ECIS) method to investigate the impact of EPLIN-α over-expression on cell motility. As shown in Figure 4A, EPLIN-α over-expressing breast cancer cells showed a dramatic slowdown in recovery after electric wounding. Using ECIS-RbA modelling system, it was shown that EPLIN-α over-expression in the MDAMB231EPLINexp cells resulted in a significant reduction in both resistance and capacitance, when compared with both the wild type cells and the control cells (figure 4B and 4C).

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