Limits...
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.

Show MeSH

Related in: MedlinePlus

a: EPLIN-α and its correlation with predicted prognosis (left) and clinical outcome (right). The predicted prognosis was based on the NPI value of each patient and that good, moderate and poor prognosis had NPI value either < 3.4, 3.4–5.4 or > 5.4. * p = 0.0081 vs good prognostic group. b. Levels of EPLIN-α transcript and clinical outcome. * p = 0.0003, # p = 0.0008 vs disease free patients. c and d: levels of EPLIN-α transcript and overall survival (c) and disease free survival (d). Patients with high levels of EPLIN-α transcript had a significantly longer overall (p = 0.0461, in c) and disease-free survival (p = 0.0345, in d) than those with low levels of the transcript. Inserts in a and b are values of EPLIN-α transcript that have been normalised by CK19 (shown as EPLIN:CK19 ratio).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2553413&req=5

Figure 2: a: EPLIN-α and its correlation with predicted prognosis (left) and clinical outcome (right). The predicted prognosis was based on the NPI value of each patient and that good, moderate and poor prognosis had NPI value either < 3.4, 3.4–5.4 or > 5.4. * p = 0.0081 vs good prognostic group. b. Levels of EPLIN-α transcript and clinical outcome. * p = 0.0003, # p = 0.0008 vs disease free patients. c and d: levels of EPLIN-α transcript and overall survival (c) and disease free survival (d). Patients with high levels of EPLIN-α transcript had a significantly longer overall (p = 0.0461, in c) and disease-free survival (p = 0.0345, in d) than those with low levels of the transcript. Inserts in a and b are values of EPLIN-α transcript that have been normalised by CK19 (shown as EPLIN:CK19 ratio).

Mentions: We have used the Nottingham Prognostic Index (NPI) as an indicator to assess the relationship between EPLIN-α transcript and a predicted prognosis. Patients were divided into three groups, good, moderate and poor prognosis, based on the NPI values. It was found that patients with poor prognostic index had the lowest levels of EPLIN-α (figure 2 left) amongst three groups. The difference between patients with poor prognosis and good prognosis was highly significant (p = 0.0081) (figure 2a).


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)

a: EPLIN-α and its correlation with predicted prognosis (left) and clinical outcome (right). The predicted prognosis was based on the NPI value of each patient and that good, moderate and poor prognosis had NPI value either < 3.4, 3.4–5.4 or > 5.4. * p = 0.0081 vs good prognostic group. b. Levels of EPLIN-α transcript and clinical outcome. * p = 0.0003, # p = 0.0008 vs disease free patients. c and d: levels of EPLIN-α transcript and overall survival (c) and disease free survival (d). Patients with high levels of EPLIN-α transcript had a significantly longer overall (p = 0.0461, in c) and disease-free survival (p = 0.0345, in d) than those with low levels of the transcript. Inserts in a and b are values of EPLIN-α transcript that have been normalised by CK19 (shown as EPLIN:CK19 ratio).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: a: EPLIN-α and its correlation with predicted prognosis (left) and clinical outcome (right). The predicted prognosis was based on the NPI value of each patient and that good, moderate and poor prognosis had NPI value either < 3.4, 3.4–5.4 or > 5.4. * p = 0.0081 vs good prognostic group. b. Levels of EPLIN-α transcript and clinical outcome. * p = 0.0003, # p = 0.0008 vs disease free patients. c and d: levels of EPLIN-α transcript and overall survival (c) and disease free survival (d). Patients with high levels of EPLIN-α transcript had a significantly longer overall (p = 0.0461, in c) and disease-free survival (p = 0.0345, in d) than those with low levels of the transcript. Inserts in a and b are values of EPLIN-α transcript that have been normalised by CK19 (shown as EPLIN:CK19 ratio).
Mentions: We have used the Nottingham Prognostic Index (NPI) as an indicator to assess the relationship between EPLIN-α transcript and a predicted prognosis. Patients were divided into three groups, good, moderate and poor prognosis, based on the NPI values. It was found that patients with poor prognostic index had the lowest levels of EPLIN-α (figure 2 left) amongst three groups. The difference between patients with poor prognosis and good prognosis was highly significant (p = 0.0081) (figure 2a).

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