Document Detail

Determinants of glutamine dependence and utilization by normal and tumor-derived breast cell lines.
MedLine Citation:
PMID:  9618156     Owner:  NLM     Status:  MEDLINE    
A continual supply of the amino acid glutamine (GLN) may be necessary for cancerous cell growth. GLN plays a central role in multiple metabolic pathways and has long been considered an essential component of tissue culture media. However, the GLN requirements of tumor cell lines and the factors that determine a cell's need for GLN have not been comprehensively studied. Also, it remains unclear how various metabolic pathways contribute to GLN consumption. In the present study, possible determinants of GLN metabolism were examined in seven breast cell lines, two derived from immortalized normal tissue and five of tumor origin. These cells exhibited different dependencies on media GLN concentration for growth and a wide range of GLN utilization rates. GLN uptake was facilitated by a single, common transporter functionally defined as System ASC. However, the affinities for GLN exhibited by this transporter differed appreciably between cell lines. Furthermore, the concentration at which media GLN became a limiting factor for cellular proliferation correlated with transporter affinity. The origin of the cell lines was not a determinant of GLN metabolism because immortalized cells of nontumor origin exhibited GLN dependence and utilization rates comparable to those of tumor-derived cells. The rates of CO2 production from GLN were similar for each cell lines. Rates of GLN disappearance and glutamate appearance in media were strongly correlated, with 32-80% of media GLN converted to glutamate. Both rates were directly affected by media cystine concentration, suggesting that a large portion of glutamate efflux was coupled with cystine import through the amino acid transport system x(c)-. These results demonstrated that cell growth is a function of GLN influx and suggest that GLN is used to supply glutamate and cystine, perhaps for glutathione synthesis.
C L Collins; M Wasa; W W Souba; S F Abcouwer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  176     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-07-01     Completed Date:  1998-07-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  166-78     Citation Subset:  IM    
Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
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MeSH Terms
Biological Transport / physiology
Breast Neoplasms / metabolism*
Carbon Dioxide / metabolism
Cell Division / drug effects
Culture Media / chemistry
Cystine / pharmacokinetics
Glutamic Acid / metabolism
Glutamine / metabolism*
Glutathione / biosynthesis
Sodium / pharmacology
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Culture Media; 124-38-9/Carbon Dioxide; 56-85-9/Glutamine; 56-86-0/Glutamic Acid; 56-89-3/Cystine; 70-18-8/Glutathione; 7440-23-5/Sodium

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