title: Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer.
abstract: BACKGROUND
  L-type amino acid transporter 1 (LAT1) is highly expressed in various human neoplasms. Antitumor activity of inhibiting LAT1 was analyzed in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Expression of LAT1 mRNA in 54 lung cancer cell lines was examined by RT-PCR. An inhibitor of LAT1, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), was administered to H1395 cell. LAT1 expression was examined in correlation with clinical features and outcome in 51 NSCLC patients.
  
  
  RESULTS
  Inhibition of LAT1 by BCH reduced cell viability in H1395 cells. Furthermore, co-administration of gefitinib with BCH reduced the viability of the cells more than either agent alone. Inhibition of LAT1 reduced the level of phosphorylation of mTOR, p70S6K and 4EBP1. LAT1 protein expression was closely associated with wild type EGFR, and was an independent significant factor to predict a poor prognosis.
  
  
  CONCLUSIONS
  Inhibition of LAT1 may be a new rationale to the effective therapy of NSCLC without EGFR mutation.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Imai
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Noboru
authors.initials: N
authors.lastname: Oriuchi
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Shimizu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tominaga
authors.forename: Noriko
authors.initials: N
authors.lastname: Yanagitani
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sunaga
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Shushi
authors.initials: S
authors.lastname: Nagamori
authors.forename: Kanyarat
authors.initials: K
authors.lastname: Promchan
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000598:Amino Acids, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D027261:Fusion Regulatory Protein-1 / Q000096:biosynthesis / Q000235:genetics; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D027283:Large Neutral Amino Acid-Transporter 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000598:Amino Acids, Cyclic; D027261:Fusion Regulatory Protein-1; D027283:Large Neutral Amino Acid-Transporter 1; D011799:Quinazolines; D012333:RNA, Messenger; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; C546842:MTOR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D000077156:Gefitinib