Skip to main content

Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia.

Publication ,  Journal Article
Kung, H-N; Marks, JR; Chi, J-T
Published in: PLoS Genet
August 2011

Although significant variations in the metabolic profiles exist among different cells, little is understood in terms of genetic regulations of such cell type-specific metabolic phenotypes and nutrient requirements. While many cancer cells depend on exogenous glutamine for survival to justify the therapeutic targeting of glutamine metabolism, the mechanisms of glutamine dependence and likely response and resistance of such glutamine-targeting strategies among cancers are largely unknown. In this study, we have found a systematic variation in the glutamine dependence among breast tumor subtypes associated with mammary differentiation: basal- but not luminal-type breast cells are more glutamine-dependent and may be susceptible to glutamine-targeting therapeutics. Glutamine independence of luminal-type cells is associated mechanistically with lineage-specific expression of glutamine synthetase (GS). Luminal cells can also rescue basal cells in co-culture without glutamine, indicating a potential for glutamine symbiosis within breast ducts. The luminal-specific expression of GS is directly induced by GATA3 and represses glutaminase expression. Such distinct glutamine dependency and metabolic symbiosis is coupled with the acquisition of the GS and glutamine independence during the mammary differentiation program. Understanding the genetic circuitry governing distinct metabolic patterns is relevant to many symbiotic relationships among different cells and organisms. In addition, the ability of GS to predict patterns of glutamine metabolism and dependency among tumors is also crucial in the rational design and application of glutamine and other metabolic pathway targeted therapies.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

August 2011

Volume

7

Issue

8

Start / End Page

e1002229

Location

United States

Related Subject Headings

  • Promoter Regions, Genetic
  • Phenotype
  • Nutritional Physiological Phenomena
  • Molecular Targeted Therapy
  • Humans
  • Glutamine
  • Glutaminase
  • Glutamate-Ammonia Ligase
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kung, H.-N., Marks, J. R., & Chi, J.-T. (2011). Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia. PLoS Genet, 7(8), e1002229. https://doi.org/10.1371/journal.pgen.1002229
Kung, Hsiu-Ni, Jeffrey R. Marks, and Jen-Tsan Chi. “Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia.PLoS Genet 7, no. 8 (August 2011): e1002229. https://doi.org/10.1371/journal.pgen.1002229.
Kung, Hsiu-Ni, et al. “Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia.PLoS Genet, vol. 7, no. 8, Aug. 2011, p. e1002229. Pubmed, doi:10.1371/journal.pgen.1002229.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

August 2011

Volume

7

Issue

8

Start / End Page

e1002229

Location

United States

Related Subject Headings

  • Promoter Regions, Genetic
  • Phenotype
  • Nutritional Physiological Phenomena
  • Molecular Targeted Therapy
  • Humans
  • Glutamine
  • Glutaminase
  • Glutamate-Ammonia Ligase
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling