IGF-I receptor gene activation enhanced the expression of monocarboxylic acid transporter 1 in hepatocarcinoma cells.

The present study aims to investigate the effect of IGF-I receptor (IGF-IR) gene activation on the expression of monocarboxylic acid transporters (MCTs) in hepatocarcinoma cells. In order to reflect malignant hepatoma, H4IIE cells (a rat hepatoma cell line) stably expressing IGF-IR (IGF-IR-H4IIE cells) have been established by retroviral infection and then the effect of IGF-IR gene up-regulation on the modulation of MCT expression was determined in IGF-IR-H4IIE cells. Immunoblot assay indicated that the expression level of MCT1 was 3.3-fold higher in IGF-IR-H4IIE cells compared to that in control cells, implying that IGF-IR signaling is coupled with the process of MCT1 expression. In contrast, the expression level of MCT2 was not affected by the IGF-IR activation, suggesting that MCT1 and MCT2 are regulated by the distinct type of signals. Furthermore, the cellular uptake of benzoic acid, a representative substrate of MCT1, was significantly (p<0.05) enhanced following the activation of IGF-IR via the pre-incubation with IGF-I (10 ng/ml). In conclusion, MCT1 expression was up-regulated in hepatocarcinoma cells and the IGF-IR signaling appeared to be coupled with the modulation of MCT1 expression.