title: L-type amino acid transporter 1 (LAT1): a new therapeutic target for canine mammary gland tumour.
abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities, such as cellular growth, proliferation and maintenance. LAT1 has recently received attention because of its preferential and upregulated expression in a variety of human tumours which is in contrast to its limited distribution and low-level expression in normal tissues. In this study, the feasibility of using an LAT1 inhibitor as a new therapeutic agent was explored for mammary gland tumours (MGT). [(3)H]l-leucine uptake by CHM, a cell line established from MGT, and effects on cell growth were analysed in the presence or absence of two LAT1 inhibitors, namely, BCH (2-amino-2-norbornane-carboxylic acids) or melphalan (LPM). [(3)H]l-leucine uptake and cellular growth activities in CHM were inhibited in a dose-dependent manner by both LAT1 inhibitors. The inhibitory growth activities of various conventional anti-cancer drugs used for MGT treatment, including carboplatin, cyclophosphamide, doxorubicin, mitoxantrone, vinblastine and vincristine, were significantly enhanced by combining use with BCH or LPM. The findings suggest that LAT1 could be a new therapeutic target for canine MGT.
authors.affiliation: Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Hanazono
authors.forename: Takahiro
authors.initials: T
authors.lastname: Komatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kadosawa
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Iwano
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Uchide
mesh_terms: D000598:Amino Acids, Cyclic / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western / Q000662:veterinary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008558:Melphalan / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary
chemical_list: D000598:Amino Acids, Cyclic; D000970:Antineoplastic Agents; D027283:Large Neutral Amino Acid-Transporter 1; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D008558:Melphalan
keywords: Dog; L-type amino acid transporter 1 (LAT1); Mammary tumour; Oncology; Transporter