Document Detail

Differential expression and functional characterization of system L amino acid transporters in human normal osteoblast cells and osteogenic sarcoma cells.
MedLine Citation:
PMID:  16827134     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The amino acid transport system L is a major nutrient transport system responsible for Na(+)-independent transport of neutral amino acids, including several essential amino acids. The system L is divided into two major subgroups, the L-type amino acid transporter 1 (LAT1) and the L-type amino acid transporter 2 (LAT2). In malignant tumors, the LAT1 is highly expressed to support tumor cell growth. In the present study, the expressions and functions of the system L amino acid transporters were examined and compared in both FOB human osteoblast cells and Saos2 human osteogenic sarcoma cells. MATERIALS AND METHODS: The expressions and functions of the system L amino acid transporters in both FOB and Saos2 cells were examined using RT-PCR, Western blot analysis and amino acid transport measurement. RESULTS: RT-PCR and Western blot analysis revealed that the FOB and Saos2 cells expressed LAT1 and LAT2, together with their associated protein 4F2hc, but the expression of LAT2 in the Saos2 cells was very weak. The uptakes of [14C]L-leucine by FOB and Saos2 cells were Na(+)-independent and were completely inhibited by the system L selective inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). The affinity and the inhibition profiles of [14C]L-leucine uptake by various amino acids in the FOB and Saos2 cells were comparable with those for the LAT2 and LAT1 expressed in Xenopus oocytes, respectively. The majority of [14C]L-leucine uptake is, therefore, mediated by LAT2 and LAT1 in FOB and Saos2 cells, respectively. CONCLUSION: These results suggest that the transport of neutral amino acids, including several essential amino acids into the FOB and Saos2 cells, are mainly mediated by LAT2 and LAT1, respectively. Moreover, the specific inhibition of LAT1 in tumor cells might be a new rationale for antitumor therapy.
Su-Gwan Kim; Hyun-Ho Kim; Hak-Kyun Kim; Chang-Hyun Kim; Hong Sung Chun; Yoshikatsu Kanai; Hitoshi Endou; Do Kyung Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  26     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2006 May-Jun
Date Detail:
Created Date:  2006-07-07     Completed Date:  2006-08-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1989-96     Citation Subset:  IM    
Departments of Oral and Maxillofacial Surgery Chosun University College of Dentistry, Kwangju 501-759, Korea.
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MeSH Terms
Amino Acid Transport System L / antagonists & inhibitors,  biosynthesis,  metabolism*
Amino Acid Transport System y+ / biosynthesis,  metabolism
Amino Acids / metabolism,  pharmacology
Amino Acids, Cyclic / pharmacology
Antigens, CD98 Light Chains / biosynthesis,  metabolism
Bone Neoplasms / metabolism*
Carbon Radioisotopes
Cell Line, Tumor
Large Neutral Amino Acid-Transporter 1 / biosynthesis,  metabolism
Leucine / metabolism,  pharmacokinetics
Osteoblasts / metabolism*
Osteosarcoma / metabolism*
Reg. No./Substance:
0/Amino Acid Transport System L; 0/Amino Acid Transport System y+; 0/Amino Acids; 0/Amino Acids, Cyclic; 0/Antigens, CD98 Light Chains; 0/Carbon Radioisotopes; 0/Large Neutral Amino Acid-Transporter 1; 0/SLC7A8 protein, human; 20448-79-7/2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; 61-90-5/Leucine

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