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dc.contributor.authorLee, Sen_US
dc.contributor.authorSyed, Nen_US
dc.contributor.authorTaylor, Jen_US
dc.contributor.authorSmith, Pen_US
dc.contributor.authorGriffin, Ben_US
dc.contributor.authorBaens, Men_US
dc.contributor.authorBai, Men_US
dc.contributor.authorBourantas, Ken_US
dc.contributor.authorStebbing, Jen_US
dc.contributor.authorNaresh, Ken_US
dc.contributor.authorNelson, Men_US
dc.contributor.authorTuthill, Men_US
dc.contributor.authorBower, Men_US
dc.contributor.authorHatzimichael, Een_US
dc.contributor.authorCrook, Ten_US
dc.identifier.citationBRITISH JOURNAL OF CANCER, 2010, 103 pp. 265 - 274en_US
dc.description.abstractBACKGROUND: The mitogen-activated protein kinase (MAPK) phosphatases or dual specificity phosphatases (DUSPs) are a family of proteins that catalyse the inactivation of MAPK in eukaryotic cells. Little is known of the expression, regulation or function of the DUSPs in human neoplasia. METHODS: We used RT-PCR and quantitative PCR (qPCR) to examine the expression of DUSP16 mRNA. The methylation in the DUSP16 CpG island was analysed using bisulphite sequencing and methylation-specific PCR. The activation of MAPK was determined using western blotting with phospho-specific antibodies for extra-cellular signal-related kinase (ERK), p38 and c-Jun N-terminal kinase (JNK). The proliferation of cell lines was assessed using the CellTiter 96 Aqueous One assay. RESULTS: The expression of DUSP16, which inactivates MAPK, is subject to methylation-dependent transcriptional silencing in Burkitt’s Lymphoma (BL) cell lines and in primary BL. The silencing is associated with aberrant methylation in the CpG island in the 50 regulatory sequences of the gene blocking its constitutive expression. In contrast to BL, the CpG island of DUSP16 is unmethylated in other non-Hodgkin’s lymphomas (NHLs) and epithelial malignancies. In BL cell lines, neither constitutive nor inducible ERK or p38 activity varied significantly with DUSP16 status. However, activation of JNK was increased in lines with DUSP16 methylation. Furthermore, methylation in the DUSP16 CpG island blocked transcriptional induction of DUSP16, thereby abrogating a normal physiological negative feedback loop that limits JNK activity, and conferred increased cellular sensitivity to agents, such as sorbitol and anthracycline chemotherapeutic agents that activate JNK. CONCLUSION: DUSP16 is a new epigenetically regulated determinant of JNK activation in BL. British Journal of Cancer (2010) 103, 265-274. doi: 10.1038/sj.bjc.6605711 Published online 15 June 2010 (C) 2010 Cancer Research UKen_US
dc.format.extent265 - 274en_US
dc.titleDUSP16 is an epigenetically regulated determinant of JNK signalling in Burkitt’s lymphomaen_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
pubs.notesaffiliation: Crook, T (Reprint Author), Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, Dept Med Oncol, London, England. Stebbing, J.; Crook, T., Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, Dept Med Oncol, London, England. Lee, S.; Syed, N.; Taylor, J.; Smith, P., Inst Canc Res, Lab Canc Genet & Epigenet, London SW3 6JB, England. Griffin, B., Univ London Imperial Coll Sci Technol & Med, Dept Virol, Sch Med, London, England. Baens, M., Katholieke Univ Leuven, Flanders Interuniv Inst Biotechnol VIB, Dept Human Genet, Human Genome Lab, B-3000 Louvain, Belgium. Bai, M., Univ Hosp Ioannina, Dept Pathol, Ioannina, Greece. Bourantas, K.; Hatzimichael, E., Univ Hosp Ioannina, Dept Hematol, Ioannina, Greece. Naresh, K., Hammersmith Hosp, Dept Pathol, London W9, England. Nelson, M., Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Dept HIV Med, London, England. Tuthill, M.; Bower, M., Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Dept Oncol, London, England. keywords: DUSP; Epigenetics; HIV; Burkitt’s lymphoma keywords-plus: ACUTE LYMPHOBLASTIC-LEUKEMIA; KINASE; CANCER; HYPERMETHYLATION; DIAGNOSIS; DELETIONS; 12P12-13; GENE; 12P research-areas: Oncology web-of-science-categories: Oncology author-email: orcid-numbers: Hatzimichael, Eleftheria/0000-0002-4408-5646 Bower, Mark/0000-0002-4077-6351 Naresh, Kikkeri/0000-0003-3807-3638 funding-acknowledgement: Cancer Research UK; Breakthrough Breast Cancer funding-text: We thank Professors D Crawford, P Farrell, M Dyer and P Degan for the supply of cell lines. The study was supported by Cancer Research UK and Breakthrough Breast Cancer. number-of-cited-references: 23 times-cited: 15 usage-count-last-180-days: 1 usage-count-since-2013: 7 journal-iso: Br. J. Cancer doc-delivery-number: 625JV unique-id: ISI:000279892300016 oa: gold_or_bronze da: 2018-08-21en_US
pubs.notesNot knownen_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorCrook, Timothyen_US

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