[Amino acid transporter molecule as a drug target].
Amino acids, especially essential amino acids are required for protein synthesis and as energy sources in all living cells. Since most amino acids are hydrophilic, special membrane proteins are necessary for their transmembrane transport particularly in transformed cells. We cloned a cDNA encoding L-type amino acid transporter, and named it LAT1. LAT1 is highly expressed in most tumor cells and in a few normal tissues such as the bone marrow, spleen, placenta and brain. As a homolog of LAT1, we also cloned LAT2 which is expressed in various normal tissues. In order to clarify the role of LAT1 in tumor cells, we tested a relatively specific inhibitor to LAT1, BCH (2-aminobicyclo-2(2,2,1)-heptane-2-caboxylic acid), and found that BCH inhibited mortality of mice treated with sarcoma cells. In addition, BCH also suppressed strongly T24 carcinoma cell growth. Moreover, LAT1 transports amino acid mimetic drugs. Thus, these results indicate that amino acid transporter molecule such as LAT1 can be a drug target.
Endou
H
H
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Kanai
Y
Y
D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000032:analysis* / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000032:analysis*; D051379:Mice; D012510:Sarcoma 180 / Q000473:pathology; D014981:Xenopus
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000598:Amino Acids, Cyclic; D002352:Carrier Proteins; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid