Document Detail


Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer.
MedLine Citation:
PMID:  21187458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
MATERIALS AND 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.
CONCLUSION: Inhibition of LAT1 may be a new rationale to the effective therapy of NSCLC without EGFR mutation.
Authors:
Hisao Imai; Kyoichi Kaira; Noboru Oriuchi; Kimihiro Shimizu; Hideyuki Tominaga; Noriko Yanagitani; Noriaki Sunaga; Tamotsu Ishizuka; Shushi Nagamori; Kanyarat Promchan; Takashi Nakajima; Nobuyuki Yamamoto; Masatomo Mori; Yoshikatsu Kanai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-28     Completed Date:  2011-02-04     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4819-28     Citation Subset:  IM    
Affiliation:
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39 Showa-machi, Maebashi, Gunma 371-8511, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Amino Acids, Cyclic / administration & dosage,  pharmacology*
Antigens, CD98 / biosynthesis,  genetics
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Carcinoma, Non-Small-Cell Lung / drug therapy*,  metabolism,  pathology
Cell Growth Processes / drug effects
Cell Line, Tumor
Humans
Immunohistochemistry
Large Neutral Amino Acid-Transporter 1 / biosynthesis,  genetics,  metabolism*
Leucine / pharmacokinetics
Lung Neoplasms / drug therapy*,  metabolism,  pathology
Middle Aged
Mutation
Quinazolines / administration & dosage
RNA, Messenger / biosynthesis,  genetics
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  genetics
TOR Serine-Threonine Kinases / antagonists & inhibitors,  metabolism
Chemical
Reg. No./Substance:
0/Amino Acids, Cyclic; 0/Antigens, CD98; 0/Large Neutral Amino Acid-Transporter 1; 0/Quinazolines; 0/RNA, Messenger; 20448-79-7/2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; 61-90-5/Leucine; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.10.1/Receptor, Epidermal Growth Factor; S65743JHBS/gefitinib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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