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pp.41-52
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.
