Document Detail


L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors.
MedLine Citation:
PMID:  16496379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
L-type amino acid transporter 1 (LAT1) is a Na+-independent neutral amino acid transport agency and essential for the transport of large neutral amino acids. LAT1 has been identified as a light chain of the CD98 heterodimer from C6 glioma cells. LAT1 also corresponds to TA1, an oncofetal antigen that is expressed primarily in fetal tissues and cancer cells. We have investigated for the first time, the expression of the transporter in the human primary astrocytic tumor tissue from 60 patients. LAT1 is unique because it requires an additional single membrane spanning protein, the heavy chain of 4F2 cell surface antigen (4F2hc), for its functional expression. 4F2hc expression was also determined by immunohistochemistry. Kaplan-Meier analyses demonstrated that high LAT1 expression correlated with poor survival for the study group as a whole (p<0.0001) and for those with glioblastoma multiforme in particular (p=0.0001). Cox regression analyses demonstrated that LAT1 expression was one of significant predictors of outcome, independent of all other variables. On the basis of these findings, we also investigated the effect of the specific inhibitor to LAT1, 2-aminobicyclo-2 (2,2,1)-heptane-2-carboxylic acid (BCH), on the survival of C6 glioma cells in vitro and in vivo using a rat C6 glioma model. BCH inhibited the growth of C6 glioma cells in vitro and in vivo in a dose-dependent manner. Kaplan-Meier survival data of rats treated with BCH were significant. These findings suggest that LAT1 could be one of the molecular targets in glioma therapy.
Authors:
Hiroshi Nawashiro; Naoki Otani; Nariyoshi Shinomiya; Shinji Fukui; Hidetoshi Ooigawa; Katsuji Shima; Hirotaka Matsuo; Yoshikatsu Kanai; Hitoshi Endou
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  119     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-05-15     Completed Date:  2006-07-28     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  484-92     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2006 Wiley-Liss, Inc.
Affiliation:
Department of Neurosurgery, National Defense Medical College, Tokorozawa, Saitama, Japan. nawa1957@ndmc.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Amino Acids, Cyclic / pharmacology
Animals
Antigens, CD98 Heavy Chain / analysis
Astrocytoma / metabolism,  pathology*
Brain Neoplasms / metabolism,  pathology*
Cell Line, Tumor
Cell Survival / drug effects
Child
Female
Glioma / drug therapy,  mortality,  pathology
Humans
Immunohistochemistry
Infant, Newborn
Large Neutral Amino Acid-Transporter 1 / analysis*
Male
Middle Aged
Neoplasms, Experimental / drug therapy,  mortality,  pathology
Rats
Rats, Wistar
Survival Analysis
Survival Rate
Chemical
Reg. No./Substance:
0/Amino Acids, Cyclic; 0/Antigens, CD98 Heavy Chain; 0/Large Neutral Amino Acid-Transporter 1; 20448-79-7/2-aminobicyclo(2,2,1)heptane-2-carboxylic acid

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


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