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Inhibition of glutaminase expression by antisense mRNA decreases growth and tumourigenicity of tumour cells
Open accessAbstract
Phosphate-activated glutaminase has a critical role in tumours and rapidly dividing cells and its activity is correlated with malignancy. Ehrlich ascites tumour cells transfected with the pcDNA3 vector containing an antisense segment (0.28 kb) of rat kidney glutaminase showed impairment in the growth rate and plating efficiency, as well as a shortage in the glutaminase protein and activity. The C-terminal segment used is well conserved in all glutaminase sequences known. The transfected cells, named 0.28AS-2, displayed remarkable changes in their morphology compared with the parental cell line. The 0.28AS-2 cells also lost their tumourigenic capacity in vivo. Control mice developed an ascitic tumour, with a lifespan of 16±1 days, when inoculated with 107 cells/mouse; on the contrary, animals inoculated with transfected cells up to 2.5 times the cell numbers of control mice did not develop tumours and behaved as healthy animals. The ability to revert the transformed phenotype of antisense-transfected cells confirms the relevance of glutaminase in the transformation process and could provide new ways for the study of gene therapy.
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“specific genetic interference with glutaminase (GLS) inhibits tumor cell growth13.”
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“GLS overexpression has been observed in different tumor cells, and these enzymes are found to function in the metabolic reprogramming of glutamine addiction in cancer198.”
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Metadata
- Authors
- LOBO, C., RUIZ-BELLIDO, M. A., ALEDO, J. C., MÁRQUEZ, J., NÚÑEZ DE CASTRO, I., & ALONSO, F. J.
- Affiliations
- Universidad de Málaga (ES)
- Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Campus de Teatinos, Universidad de Málaga, 29071 Málaga, Spain
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2000-05-23
- Volume
- 348
- Issue
- 2
- Pages
- 257-261
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1221061
- OpenAlex
- W1998424488
- Cited by
- 151
- References
- 30
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 13 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 9 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 9 · 2013: 8 · 2012: 8
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- glutaminase, antisense RNA, phosphate-activated glutaminase, Ehrlich ascites tumor cells, tumor growth inhibition, tumorigenicity, gene therapy, cell transformation, plating efficiency, cell morphology
- MeSH terms
- Animals, Carcinoma, Ehrlich Tumor, Cell Division, Glutaminase, Kidney, Kinetics, RNA, Messenger, Transfection, Tumor Cells, Cultured, Tumor Stem Cell Assay, Gene Expression Regulation, Enzymologic, RNA, Antisense, Mice, Rats
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