Retinoic Acid Actions Are Connected with Downregulation of ENO1 Gene Products in the Follicular Thyroid Carcinoma Cell Line FTC-133

Enolases (2-phospho-D-glycerate hydrolases) have been characterized as glycolytic enzymes that catalyse the interconversion of 2-phosphoglycerate to phosphoenolpyruvate and may be involved in development and differentiation. Various tumors are known to display increased enolase expression and enolase seems to be involved in tumor progression. A single human ENO1 transcript encodes two proteins of 48 kDa and 37 kDa (MBP-1), both are discussed to participate in the down-regulation of c-myc expression. In this study we investigated the influence of retinoic acid (RA) on (a) the expression of both ENO1 gene products and (b) the proteome pattern in the follicular thyroid carcinoma cell line FTC-133. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed an initial increase in ENO1 expression at 24h and 48h followed by a subsequent decrease at 72h following RA stimulation. ENO1 proteins were downregulated by RA at all incubation times tested. The downregulation of ENO1 protein correlated with RA-induced reduction in ATP levels and phosphorylation status in FTC-133. Moreover, RA treatment downregulated c-myc protein expression and decreased proliferation of FTC-133 cells. Two dimensional gel analyses revealed a significant RA-induced alteration in proteome profile in FTC-133. In summary, our data show that RA downregulates both ENO1 gene products at 48 kDa and 37 kDa in FTC-133. Thus, RA may potentially impair the metastatic potential of FTC-133 cells by different mechanisms including decrease in metabolism and proliferation and these effects could in part be mediated by a downregulation of c-Myc.