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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Specific genetic interference with glutaminase (GLS) inhibits tumor cell growth.
“specific genetic interference with glutaminase (GLS) inhibits tumor cell growth13.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [13]
GLS overexpression is observed in different tumor cells and functions in metabolic reprogramming of glutamine addiction.
“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.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [198]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · see citing works
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078 · see citing works
(1985) · International Journal of Biochemistry · doi:10.1016/0020-711x(85)90098-9 · Cited by 3,497 · see citing works
Greider, C. W. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.002005 · Cited by 1,021 · see citing works
Glycolysis, glutaminolysis and cell proliferation
McKeehan, W. L. (1982) · Cell Biology International Reports · doi:10.1016/0309-1651(82)90125-4 · Cited by 305 · see citing works
Souba, W. W. (1993) · Annals of Surgery · doi:10.1097/00000658-199312000-00004 · Cited by 294 · see citing works
Glutamine Metabolism in Mammalian Tissues
Häussinger, D., & Sies, H. (1984) · Springer eBooks · doi:10.1007/978-3-642-69754-8 · Cited by 240 · see citing works
Anticancer Drug Development: Preclinical Screening, Clinical Trials and Approval
Selwood, D. L. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602070 · Cited by 238 · see citing works
Relevance of glutamine metabolism to tumor cell growth
Medina, M. Á., Sánchez‐Jiménez, F., Márquez, J., Quesada, A. R., & de Castro, I. N. (1992) · Molecular and Cellular Biochemistry · doi:10.1007/bf00230880 · Cited by 186 · see citing works
Self-citationA Quantitative Approach to Metabolic Control
Crabtree, B., & Newsholme, E. A. (1985) · Current topics in cellular regulation · doi:10.1016/b978-0-12-152825-6.50006-0 · Cited by 142 · see citing works
Nitrogen movement between host and tumor in mice inoculated with Ehrlich ascitic tumor cells.
Carrascosa, J. M., Martínez, P., & de Castro, I. N. (1984) · PubMed · Cited by 95 · see citing works
Shapiro, R. A., Farrell, L. E., Srinivasan, M., & Curthoys, N. P. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55132-2 · Cited by 94 · see citing works
Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase
GÓMEZ-FABRE, P. M., Aledo, J. C., CASTILLO-OLIVARES, A. D., Alonso, F. J., de Castro, I. N., Campos-Sandoval, J. A., & Márquez, J. (2000) · Biochemical Journal · doi:10.1042/bj3450365 · Cited by 93 · see citing works
Self-citationEarhart, R. H., Amato, D. J., Chang, A. Y.-C., Borden, E. C., Shiraki, M., Dowd, M. E., Comis, R. L., Davis, T. E., & Smith, T. J. (1990) · Investigational New Drugs · doi:10.1007/bf00216936 · Cited by 71 · see citing works
Asparaginase as a drug for treatment of acute lymphoblastic leukaemia.
Gallagher, M. P., Marshall, R., & Wilson, R. K. (1989) · PubMed · Cited by 63 · see citing works
Hepatic glutaminase expression: relationship to kidney‐type glutaminase and to the urea cycle
Watford, M. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.15.8262331 · Cited by 61 · see citing works
Phosphate‐activated glutaminase expression during tumor development
Aledo, J. C., Segura, J. A., Medina, M. Á., Alonso, F. J., de Castro, I. N., & Márquez, J. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)80236-x · Cited by 54 · see citing works
Self-citationQuesada, A. R., Medina, M. Á., Márquez, J., Sánchez‐Jiménez, F., & de Castro, I. N. (1988) · PubMed · Cited by 52 · see citing works
Self-citationChung-Bok, M.-I., Vincent, N., Jhala, U. S., et al. (1997) · Biochemical Journal · doi:10.1042/bj3240193 · Cited by 45 · see citing works
Spittler, A., Oehler, R., Goetzinger, P., Holzer, S., Reissner, C. M., Leutmezer, F., Rath, V., Wrba, F., Fuegger, R., Boltz‐Nitulescu, G., et al. (1997) · Journal of Nutrition · doi:10.1093/jn/127.11.2151 · Cited by 42 · see citing works
Reduction of tumor growth following treatment with a glutamine antimetabolite
Chance, W. T., Cao, L., KIM, M. W., et al. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90627-3 · Cited by 41 · see citing works
Glutamine transport by vesicles isolated from tumour-cell mitochondrial inner membrane
Molina, M., Segura, J. A., Aledo, J. C., Medina, M. Á., de Castro, I. N., & Márquez, J. (1995) · Biochemical Journal · doi:10.1042/bj3080629 · Cited by 31 · see citing works
Self-citationSubmitochondrial localization and membrane topography of Ehrlich ascitic tumour cell glutaminase
Aledo, J. C., de Pedro, E., GÓMEZ-FABRE, P. M., de Castro, I. N., & Márquez, J. (1997) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(96)00189-7 · Cited by 31 · see citing works
Self-citationGlutamine synthetase and glutaminase activities in various hepatoma cells.
Matsuno, T., & Hirai, H. (1989) · PubMed · Cited by 29 · see citing works
Enzyme targets of antiglutamine agents in cancer chemotherapy
Prajda, N. (1985) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(85)90077-9 · Cited by 25 · see citing works
Aledo, J. C., Gómez‐Biedma, S., Segura, J. A., Molina, M., de Castro, I. N., & Márquez, J. (1993) · Electrophoresis · doi:10.1002/elps.1150140116 · Cited by 16 · see citing works
Self-citationTumor Glutaminase Purification
Segura, J. A., Aledo, J. C., Gómez‐Biedma, S., et al. (1995) · Protein Expression and Purification · doi:10.1006/prep.1995.1045 · Cited by 14 · see citing works
Self-citationl-Glutamine transport in native vesicles isolated from Ehrlich ascites tumor cell membranes
Medina, M. Á., Quesada, A. R., & de Castro, I. N. (1991) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf00785818 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Murray, J. A. H. and Crockett, N. (1992) in Antisense RNA and DNA (Murray, H., ed.), pp. 1-49, Wiley-Liss, New York 22
- Gallagher, M. P., Marshall, R. D. and Wilson, R. (1989) Essays in Biochemistry, vol. 24 (Marshall, R. D. and Tipton, K. F., eds.), pp. 1-40, Academic Press, London
Cited by
Sorted by citations
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124 · see citing works
Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer
DeBerardinis, R. J., & Cheng, T. (2010) · Oncogene · doi:10.1038/onc.2009.358 · Cited by 1,365 · see citing works
Glutamine and cancer: cell biology, physiology, and clinical opportunities
Hensley, C. T., Wasti, A. T., & DeBerardinis, R. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69600 · Cited by 1,262 · see citing works
Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021 · see citing works
Brick by brick: metabolism and tumor cell growth
DeBerardinis, R. J., Sayed, N., Ditsworth, D., & Thompson, C. B. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.02.003 · Cited by 1,018 · see citing works
Carr, E. L., Kelman, A., Wu, G. S., Gopaul, R., Senkevitch, E., Aghvanyan, A., Turay, A. M., & Frauwirth, K. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903586 · Cited by 830 · see citing works
Pyruvate kinase type M2 and its role in tumor growth and spreading
Mazurek, S., Boschek, C. B., Hugo, F., & Eigenbrodt, E. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.04.009 · Cited by 812 · see citing works
Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells
Mazurek, S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.02.005 · Cited by 694 · see citing works
Timmerman, L. A., Holton, T., Yuneva, M., Louie, R. J., Padró, M., Daemen, A., Hu, M., Chan, D. A., Ethier, S. P., van ‘t Veer, L. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.08.020 · Cited by 573 · see citing works
Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation
Sellers, K., Fox, M. P., Bousamra, M., Slone, S. P., Higashi, R. M., Miller, D. M., Wang, Y., Yan, J., Yuneva, M. O., Deshpande, R., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci72873 · Cited by 497 · see citing works
Pyruvate carboxylase is required for glutamine-independent growth of tumor cells
Cheng, T., Sudderth, J., Yang, C., Mullen, A. R., Jin, E. S., Matés, J. M., & DeBerardinis, R. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016627108 · Cited by 475 · see citing works
van den Heuvel, A. P. J., Jing, J., Wooster, R. F., & Bachman, K. E. (2012) · Cancer Biology & Therapy · doi:10.4161/cbt.21348 · Cited by 209 · see citing works
Thangavelu, K., Pan, C. Q., Karlberg, T., Balaji, G., Uttamchandani, M., Suresh, V., Schüler, H., Low, B. C., & Sivaraman, J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116573109 · Cited by 206 · see citing works
Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach
Chen, L., & Cui, H. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160922830 · Cited by 184 · see citing works
Lin, Y., Ma, C., Liu, C., Wang, Z., Yang, J., Liu, X., Shen, Z., & Wu, R. (2016) · Oncotarget · doi:10.18632/oncotarget.8762 · Cited by 126 · see citing works
Glutamine in neoplastic cells: Focus on the expression and roles of glutaminases
Szeliga, M., & Obara-Michlewska, M. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.01.008 · Cited by 76 · see citing works
Hoerner, C. R., Chen, V. J., & Fan, A. C. (2019) · Kidney Cancer · doi:10.3233/kca-180043 · Cited by 68 · see citing works
Lin, Y., Ma, C., Bezabeh, T., Wang, Z., Liang, J., Huang, Y., Zhao, J., Liu, X., Ye, W., Tang, W., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32190 · Cited by 57 · see citing works
Myc-induced glutaminolysis bypasses HIF-driven glycolysis in hypoxic small cell lung carcinoma cells
Thorén, M. M., Vaapil, M., Staaf, J., Planck, M., Johansson, M. E., Mohlin, S., & Påhlman, S. (2017) · Oncotarget · doi:10.18632/oncotarget.16904 · Cited by 31 · see citing works
- 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
- 28
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review