Physiological Role of L-type Amino Acid Transporter 1 in Two Lines of Cultured Choriocarcinoma Cells, JAR and JEG-3

In cells that proliferate abundantly, such as cancer cells, the expressions of many nutrient transporters increase in order to drive the uptake of required nutrients. The system L transporters are the main sodium-independent neutral amino acid transporters. They have four isoforms：L-type amino acid transporter （LAT） 1, 2, 3, and 4. The expression of LAT1 has been reported in lines of cultured choriocarcinoma cells. However, the role of LAT1 in choriocarcinomas has not been adequately clarified. This study examined the role of LAT1 in these cell lines JAR and JEG-3. Based on an examination of mRNA and protein expression, it was determined that both JAR and JEG-3 cells express LAT1. The uptake of leucine, a substrate of LATs, by JAR and JEG-3 cells showed that there are sodium-independent leucine transport. To examine whether leucine transport is mediated by LAT1, a leucine uptake was examined with loading of JPH203, a LAT1 specific inhibitor, and transport inhibition was clearly seen. Cell counts were measured to examine whether cell proliferation was decreased by JPH203 treatment. Inhibition of JEG-3 cell proliferation was seen on day 4 of the treatment. No inhibition of JAR cell proliferation was seen by low concentrations of JPH203, however inhibition was seen on a higher concentration of JPH203. JPH203 decreased cell activityconcentration-dependently in JEG-3 cells. JAR cell, however, showed an increased activity following JPH203 treatment at low concentrations. Thus, the study found that LAT1-mediated amino acid transport occurs in these two different lines of cultured choriocarcinoma cells. Moreover, it showed that the two types of cells responded differently with respect to inhibition of cell proliferation and changes in cell activity as a result of inhibition of LAT1-mediated amino acid transport. The results showed that LAT1-mediated amino acid transport in choriocarcinoma is complex and has a variety of functions.