Abstract | BACKGROUND:
Alpha-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 FINDINGS: We 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. CONCLUSIONS: 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 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.
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Authors | Mariavera Lo Presti, Arianna Ferro, Flavia Contino, Claudia Mazzarella, Silvia Sbacchi, Elena Roz, Carmelo Lupo, Giovanni Perconti, Agata Giallongo, Paola Migliorini, Antonio Marrazzo, Salvatore Feo |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 9
Pg. e12961
(Sep 23 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 20886042
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- DENND4A protein, human
- DNA-Binding Proteins
- Phosphopyruvate Hydratase
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
(genetics, metabolism)
- Breast Neoplasms
(diagnosis, genetics, metabolism, pathology)
- Carcinoma, Ductal
(diagnosis, genetics, metabolism, pathology)
- Cell Nucleus
(genetics, metabolism)
- Cytoplasm
(enzymology, genetics)
- DNA-Binding Proteins
(genetics, metabolism)
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Middle Aged
- Neoplasm Invasiveness
- Phosphopyruvate Hydratase
(genetics, metabolism)
- Prognosis
- Protein Transport
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