Nuclear myc promoter-binding protein-1 (MBP-1) expression is a prognostic factor in invasive ductal breast carcinoma

Myc Promoter-Binding Protein-1 (MBP-1) is a transcriptional repressor, generated by alternative translation of the a-enolase mRNA, that negatively regulates c-Myc gene expression (1) and plays a suppressive role on tumorogenesis (2, 3). We analyzed aenolase and MBP-1 expression and localization in normal breast epithelium and primary infiltrating ductal breast carcinoma (IDC) from 177 patients by Western blotting and immunohistochemical analyses, using specific anti-a-enolase mAbs. A significantly increase in a-enolase expression was observed in 98% of the analysed tumors, compared to normal tissues. Nuclear MBP- 1 has been found in almost all normal tissues while its expression is retained in only 35% of the matched tumours. Statistically significant inverse correlation was observed between expression and nuclear localization of MBP-1 and ErbB2 and Ki-67 expression, node positivity and tumor grade. Furthermore, nuclear MBP-1 is associated with good disease-free survival of patients with primary IDC. Transfection experiments in human breast SKBr3 cells (ErbB2+) demonstrated that MBP-1 ectopic expression results in down regulation of ErbB2 expression, and led us to identify the ErbB2 promoter region involved in the binding, indicating that, like c-Myc gene, ErbB2 is a direct target of MBP-1 transcriptional repression fuctions in breast cancer. Owing to the prognostic influence of nuclear-MBP-1 expression in a subgroup of small tumors and among patients with node-negative and ErbB2- cancers, where the need for prognostication is the greatest, MBP-1 nuclear expression may prove to be a clinically valuable prognostic variable for breast cancer patients.