Identification of a prognostic gene signature associated with MBP-1 expression in ErbB2-negative breast carcinomas

Abstract

The ENO1 transcript, which encodes the glycolitic enzyme alpha-enolase, can be translated into a shorter nuclear protein called Myc-promoter Binding Protein-1 (MBP-1) by using an alternative translation start site. MBP-1 acts as a negative regulator of c-Myc, ErbB2 and Cox2 genes (1). Several evidences indicate that MBP-1 acts as a tumor suppressor in breast carcinoma and prostate cancer and its expression results in a reduced invasive ability (2). In our previous studies, we showed that MBP-1 is expressed and easily detectable in normal breast epithelial cells, but a loss of expression occurs in most primary invasive ductal carcinomas (IDC) of the breast. Furthermore, in these tumors MBP-1 expression inversely correlated with the expression levels of the ErbB2 and Ki67 proteins (3). In order to better understand the role of MBP-1 in breast cancer and to correlate its expression to a gene signature with prognostic value, we evaluated the expression of approximately 21,000 genes in primary breast carcinoma by using the Agilent microarray technology. A comparison of the gene expression profiles obtained from MBP-1+ve and MBP-1-ve ErbB2-negative IDCs led to the identification of differentially expressed (DE) genes that may underlie the different clinical behaviors of these two subtypes of breast carcinoma. Owing to the prognostic influence of nuclear MBP-1 expression in a subgroup of tumors from patients with node-negative and ErbB2-negative carcinomas, the combination of immunohistochemical analyses of MBP-1 and proteins encoded by genes we found DE by expression profiling, may prove to be a clinically valuable prognostic variable for breast cancer patients.