Myc promoter-binding protein-1 (MBP-1) is a novel potential prognostic marker in invasive ductal breast carcinoma

• Published in: PloS one 2010-09, Vol.5 (9), p.e12961-e12961
• Main Authors: Lo Presti, Mariavera, Ferro, Arianna, Contino, Flavia, Mazzarella, Claudia, Sbacchi, Silvia, Roz, Elena, Lupo, Carmelo, Perconti, Giovanni, Giallongo, Agata, Migliorini, Paola, Marrazzo, Antonio, Feo, Salvatore
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Breast carcinoma; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; c-Myc protein; Cancer; Cancer research; Carcinoma; Carcinoma, Ductal - diagnosis; Carcinoma, Ductal - genetics; Carcinoma, Ductal - metabolism; Carcinoma, Ductal - pathology; Cell Nucleus - genetics; Cell Nucleus - metabolism; Chromosomes; Cytoplasm; Cytoplasm - enzymology; Cytoplasm - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzymes; Epithelium; ErbB-2 protein; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetics and Genomics/Gene Expression; Genomics; Glycolysis; Humans; Invasiveness; Localization; Lung cancer; Menstruation; Metabolism; Metastasis; Middle Aged; Monoclonal antibodies; Multivariate analysis; Myc protein; Neoplasm Invasiveness; Oncology/Breast Cancer; Pathology/Molecular Pathology; Patients; Phosphopyruvate hydratase; Phosphopyruvate Hydratase - genetics; Phosphopyruvate Hydratase - metabolism; Prognosis; Prostate; Protein binding; Protein Transport; Proteins; Statistical analysis; TATA-binding protein; Tissues; Transcription; Transcription (Genetics); Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012961

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. 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. 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.