| Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells. | |
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MedLine Citation:
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PMID: 12381519 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human hepatoma cells take up glutamine at rates severalfold faster than the system N-mediated transport rates observed in normal human hepatocytes. Amino acid inhibition, kinetic, Northern blotting, RT-PCR, and restriction enzyme analyses collectively identified the transporter responsible in six human hepatoma cell lines as amino acid transporter B(0) (ATB(0)), the human ortholog of rodent ASCT2. The majority of glutamine uptake in liver fibroblasts and an immortalized human liver epithelial cell line (THLE-5B) was also mediated by ATB(0). The 2.9-kb ATB(0) mRNA was equally expressed in all cell lines, whereas expression of the system A transporters ATA2 and ATA3 was variable. In contrast, the system N isoforms (SN1 and SN2) were expressed only in well-differentiated hepatomas. ATB(0) mRNA was also expressed in cirrhotic liver and adult and pediatric liver cancer biopsies but was not detectable in isolated human hepatocytes or fetal liver. Although the growth of all hepatomas was glutamine dependent, competitive inhibition of ATB(0)-mediated glutamine uptake blocked proliferation only in poorly differentiated cells lacking SN1 or SN2 expression and exhibiting low glutamine synthetase mRNA levels. |
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Authors:
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Barrie P Bode; Bryan C Fuchs; Bryan P Hurley; Jennifer L Conroy; Julie E Suetterlin; Kenneth K Tanabe; David B Rhoads; Steve F Abcouwer; Wiley W Souba |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 283 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-10-16 Completed Date: 2002-11-13 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G1062-73 Citation Subset: IM |
Affiliation:
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Surgical Oncology Research Laboratories, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. bodebp@slu.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Transport System ASC
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physiology Biological Transport Blotting, Northern Carcinoma, Hepatocellular / metabolism*, pathology Carrier Proteins / metabolism Cell Division / physiology Cells, Cultured Fibroblasts / metabolism Glutamate-Ammonia Ligase / metabolism Glutamine / metabolism, pharmacokinetics* Humans Liver / metabolism*, pathology Liver Cirrhosis / metabolism, pathology Liver Neoplasms / metabolism*, pathology Reference Values Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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1 R29 CA69505/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Transport System ASC; 0/Carrier Proteins; 0/SLC1A5 protein, human; 56-85-9/Glutamine; EC 6.3.1.2/Glutamate-Ammonia Ligase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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