Abstract
BackgroundAlpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. α-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1) originate from a single gene through the alternative use of translational starting sites. MBP-1 binds to the P2 c-myc promoter and competes with TATA-box binding protein (TBP) to suppress gene transcription. Although several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of α-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken.Methodology and FindingsWe analyzed α-enolase and MBP-1 expression in normal breast epithelium and primary invasive ductal breast carcinoma (IDC) from 177 patients by Western blot and immunohistochemical analyses, using highly specific anti-α-enolase monoclonal antibodies. A significant increase in the expression of cytoplasmic α-enolase was observed in 98% of the tumors analysed, compared to normal tissues. Nuclear MBP-1 was found in almost all the normal tissues while its expression was retained in only 35% of the tumors. Statistically significant associations were observed among the nuclear expression of MBP-1 and ErbB2 status, Ki-67 expression, node status and tumor grade. Furthermore MBP-1 expression was associated with good survival of patients with IDC.ConclusionsMBP-1 functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of IDC may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome. Nuclear MBP-1 appears to be a novel and valuable histochemical marker with potential prognostic value in breast cancer.
Highlights
Breast cancer development is the result of an accumulation of molecular abnormalities that activate oncogenes and inactivate tumor suppressor genes
Myc promoter-binding protein-1 (MBP-1) functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of invasive ductal breast carcinoma (IDC) may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome
In addition to its glycolytic function, which is primarily exerted in the cytoplasm, a-enolase has been found on the cell surface, where it functions as a plasminogen receptor, implying that membrane-bound enolase may play a role in inflammation and tissue invasion [2]
Summary
Breast cancer development is the result of an accumulation of molecular abnormalities that activate oncogenes and inactivate tumor suppressor genes. Three enolase isoforms have been found in mammalian cells, they are named a- (ENO1), b- (ENO3), and c(ENO2) enolase The expression of these isoforms is developmentally regulated in a tissue-specific manner: the ENO1 gene product is widely distributed in a variety of tissues, whereas the ENO2 and ENO3 products are primarily found in neuron/ neuroendocrine and muscle tissues, respectively. In addition to its glycolytic function, which is primarily exerted in the cytoplasm, a-enolase has been found on the cell surface, where it functions as a plasminogen receptor, implying that membrane-bound enolase may play a role in inflammation and tissue invasion [2]. Alpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. A-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1) originate from a single gene through the alternative use of translational starting sites. Several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of a-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken
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