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

AbstractBACKGROUND:
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.
AuthorsMariavera Lo Presti, Arianna Ferro, Flavia Contino, Claudia Mazzarella, Silvia Sbacchi, Elena Roz, Carmelo Lupo, Giovanni Perconti, Agata Giallongo, Paola Migliorini, Antonio Marrazzo, Salvatore Feo
JournalPloS one (PLoS One) Vol. 5 Issue 9 Pg. e12961 ( 2010) ISSN: 1932-6203 [Electronic] United States
PMID20886042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • DENND4A protein, human
  • DNA-Binding Proteins
  • Phosphopyruvate Hydratase
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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