Arrùno acid transpoπers play an important role in supplying nutrition to cells and for cell proliferation. System L is a major nutrient transport system responsible for the Na+-independent transport of large neutral amino acids including several essential amino acids. In malignant tumors, a system L transporter L-type amino acid transporter 1 (LATl) is upregulated to support tumor cell growth. In the present study, we have examined the expression and function of system L amino acid transporter in FaDu human pharyngeal squamous carcinoma cells. RT-PCR, real-time quantitative RT-PCR and westem blot analysis have revealed that the FaDu cells express LATl together with its associaω19 protem 4F2hc, whereas the FaDu cells do not express the other system L isoform L-type amino acid transporter 2 (LAT2). 까le uptake of L-(14Clleucine by FaDu cells is Na+-independent and almost completely inhibited by system L selective inhibitor 2-aminobicyclo-(2,2,1)-heptane-2- carboxylic acid (BCH). The profiles of the inhibition of L-[I4Cllellcine uptake by variolls amino acids in the FaDu cells are comparable with those for the LA T1 expressed in Xenopus 。()(찌es. π1e majority of L-[I4Clleucine uptake is, therefore, mediated by LAT1 in the FaDu cells. These results suggest that the transport of neutral amino acids including several essential amino acids in the FaDu human pharyngeal squamous carcinoma cells mediated by LAT1. In addition, specific inhibition of LAT1 by such agents as BCH in pharyngeal squamous cell carcinomas will be a new rationale for anti-cancer therapy.

It has been said that amino acid transporters play an important role in supplying nutrition to normal and cancer cells and for cell proliferation. System L is a major nutrient transport system responsible for the Na+-independent transport of large neutral amino acids including several essential amino acids. In malignant tumors, a system L transporter L-type amino acid transporter 1(LAT1) is up-regulated to support tumor cell growth. In the present study, we have examined the function of LAT1 and its expression in the KB human oral epidermoid carcinoma cells. RT-PCR, western blot analysis and immunohistochemical analysis have revealed that KB cells express LAT1 in the plasma membrane together with its associating protein 4F2hc, whereas KB cells do not express the other system L isoform LAT2. The uptake of L-[14C]leucine by KB cells is Na+-independent and almost completely inhibited by system L selective inhibitor BCH. The profiles of the inhibition of L-[14C]leucine uptake by amino acids in the KB cells are comparable with those for the LAT1 expressed in Xenopus oocytes. The majority of L-[14C]leucine uptake is, therefore, mediated by LAT1 in the KB cells. These results suggest that the uptakes of neutral amino acids including several essential amino acids in the KB oral epidermoid carcinoma cells mediated by LAT1. In addition, specific inhibition of LAT1 by such agents as BCH in human oral squamous cell carcinomas will be a new rationale for anti-cancer therapy.