Enolase-α Is Frequently Down-Regulated in Non-Small Cell Lung Cancer and Predicts Aggressive Biological Behavior

Abstract

PURPOSE: Enolase-alpha is a cytoplasmic glycolytic enzyme important in the formation of phosphoenolpyruvate. Enolase-alpha and c-myc binding protein (MBP-1) originate from a single gene through alternative use of translational starting sites. Both enolase-alpha and MBP-1 can bind to the P2 element in the c-myc promoter and compete with TATA-box binding protein (TBP) to suppress transcription of c-myc. EXPERIMENTAL DESIGN: To determine a potential role of enolase-alpha in vivo, we analyzed enolase-alpha expression in non-small cell lung cancer (NSCLC) tissues from 46 patients by Western blotting and immunohistochemical analysis. RESULTS: Twelve (26%) of the 46 tumors showed a significantly reduced enolase-alpha expression. Although no statistically significant association was observed between the down-regulation of enolase-alpha and pathological stage, tumor histology, or differentiation, the patients whose tumors showed reduced enolase-alpha expression had a significantly poorer overall survival compared with those without down-regulation of this molecule (P = 0.0398). CONCLUSIONS: Our results indicate down-regulation of enolase-alpha is common in NSCLC and may play an important role in lung tumorigenesis.