BACKGROUND: Emerging evidence supports a role for glutamate in the biology of cancer. We studied the impact of glutamate receptor subunit silencing on cancer phenotype. MATERIALS AND METHODS: Different fragments of the coding region for ionotropic glutamate receptor AMPA 4 (GLUR4), ionotropic glutamate receptor N-methyl D-aspartate 1 (NR1), ionotropic glutamate receptor kainate 5 (KA2) and ionotropic glutamate receptor N-methyl D-aspartate 2D (NR2D) were stably transfected into human TE671, RPMI8226 and A549 cell lines. Resulting changes in cell proliferation, migration and mRNA expression of genes that determine cancer phenotype were assayed. RESULTS: Decreased expression of GLUR4 markedly increased cancer cell proliferation, whereas decreased expression of NR1 markedly reduced the propensity of cancer cells to proliferate. Knockdown of KA2 and NR2D did not influence cancer phenotype. Gene silencing of GLUR4 modulated the mRNA expression of various genes in these cancer cell lines, as determined with the Human Cancer PathwayFinder™ PCR Array. Knockdown of GLUR4 influenced the expression and function of genes involved in invasion and metastasis, tumour suppressor genes, oncogenes and adhesion genes. CONCLUSION: The findings suggest that glutamate receptor subunits on cancer cells are linked to biochemical pathways that regulate malignant phenotype.
BACKGROUND: Emerging evidence supports a role for glutamate in the biology of cancer. We studied the impact of glutamate receptor subunit silencing on cancer phenotype. MATERIALS AND METHODS: Different fragments of the coding region for ionotropic glutamate receptor AMPA 4 (GLUR4), ionotropic glutamate receptor N-methyl D-aspartate 1 (NR1), ionotropic glutamate receptor kainate 5 (KA2) and ionotropic glutamate receptor N-methyl D-aspartate 2D (NR2D) were stably transfected into human TE671, RPMI8226 and A549 cell lines. Resulting changes in cell proliferation, migration and mRNA expression of genes that determine cancer phenotype were assayed. RESULTS: Decreased expression of GLUR4 markedly increased cancer cell proliferation, whereas decreased expression of NR1 markedly reduced the propensity of cancer cells to proliferate. Knockdown of KA2 and NR2D did not influence cancer phenotype. Gene silencing of GLUR4 modulated the mRNA expression of various genes in these cancer cell lines, as determined with the HumanCancer PathwayFinder™ PCR Array. Knockdown of GLUR4 influenced the expression and function of genes involved in invasion and metastasis, tumour suppressor genes, oncogenes and adhesion genes. CONCLUSION: The findings suggest that glutamate receptor subunits on cancer cells are linked to biochemical pathways that regulate malignant phenotype.
Authors: Jin Sun Cho; Na Young Kim; Jae-Kwang Shim; Ji Hae Jun; Sugeun Lee; Young-Lan Kwak Journal: Can J Anaesth Date: 2021-02-02 Impact factor: 5.063
Authors: Lisa Mirabello; Roelof Koster; Branden S Moriarity; Logan G Spector; Paul S Meltzer; Joy Gary; Mitchell J Machiela; Nathan Pankratz; Orestis A Panagiotou; David Largaespada; Zhaoming Wang; Julie M Gastier-Foster; Richard Gorlick; Chand Khanna; Silvia Regina Caminada de Toledo; Antonio S Petrilli; Ana Patiño-Garcia; Luis Sierrasesúmaga; Fernando Lecanda; Irene L Andrulis; Jay S Wunder; Nalan Gokgoz; Massimo Serra; Claudia Hattinger; Piero Picci; Katia Scotlandi; Adrienne M Flanagan; Roberto Tirabosco; Maria Fernanda Amary; Dina Halai; Mandy L Ballinger; David M Thomas; Sean Davis; Donald A Barkauskas; Neyssa Marina; Lee Helman; George M Otto; Kelsie L Becklin; Natalie K Wolf; Madison T Weg; Margaret Tucker; Sholom Wacholder; Joseph F Fraumeni; Neil E Caporaso; Joseph F Boland; Belynda D Hicks; Aurelie Vogt; Laurie Burdett; Meredith Yeager; Robert N Hoover; Stephen J Chanock; Sharon A Savage Journal: Cancer Discov Date: 2015-06-17 Impact factor: 39.397
Authors: Ping-Ching Hsu; Renny S Lan; Theodore M Brasky; Catalin Marian; Amrita K Cheema; Habtom W Ressom; Christopher A Loffredo; Wallace B Pickworth; Peter G Shields Journal: Mol Carcinog Date: 2016-08-22 Impact factor: 4.784