| L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. | |
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MedLine Citation:
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PMID: 16496379 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hiroshi Nawashiro; Naoki Otani; Nariyoshi Shinomiya; Shinji Fukui; Hidetoshi Ooigawa; Katsuji Shima; Hirotaka Matsuo; Yoshikatsu Kanai; Hitoshi Endou |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 2006-05-15 Completed Date: 2006-07-28 Revised Date: 2007-07-24 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 484-92 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2006 Wiley-Liss, Inc. |
Affiliation:
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Department of Neurosurgery, National Defense Medical College, Tokorozawa, Saitama, Japan. nawa1957@ndmc.ac.jp |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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