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SHP1 expression is epigenetically regulated and influences the sensitivity to chemotherapeutic agents in glioblastoma cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
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2012 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 14, no suppl 3, iii18-iii18 p.Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

INTRODUCTION: Glioblastoma is characterized by chemoresistance. One factor than can contribute to chemoresistance is aberrant DNA methylation of specific genes relevant for drug response, e.g. tumor suppressor genes. AIM: The aim of this study was to investigate whether the tumor suppressor gene SHP1 is epigenetically regulated and if its overexpression affects the sensitivity to chemotherapeutic drugs with different mechanisms of action in glioblastoma cell lines.

METHODS: Differences in methylation levels in the SHP1 promoter and SHP1 protein expressions between untreated cells and cells treated with the demethylating agent decitabine were analyzed with bisulfite Pyrosequencing and Western blotting. Differences in drug sensitivity to a panel of chemotherapeutic drugs with different mechanisms of action between SHP1 overexpressing clones and control clones were analyzed with the fluorometric microculture cytotoxicity assay.

RESULTS: We demonstrated that SHP1 promoter methylation was correlated to SHP1 expression and that the expression was increased upon demethylation. Overexpression of SHP1 resulted in lower (p < 0.05) sensitivity to the proteasome inhibitor bortezomib and the alkylating agents cisplatin and melphalan.

CONCLUSION: SHP1 expression may be epigenetically regulated and its overexpression influences the sensitivity to chemotherapeutic drugs in glioblastoma derived cells.

Place, publisher, year, edition, pages
2012. Vol. 14, no suppl 3, iii18-iii18 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-182415DOI: 10.1093/neuonc/nos183ISI: 000308545600067OAI: oai:DiVA.org:uu-182415DiVA: diva2:560085
Conference
10th Congress of the European-Association-of-NeuroOncology, SEP 06-09, 2012, Marseille, FRANCE
Available from: 2012-10-11 Created: 2012-10-10 Last updated: 2017-12-07Bibliographically approved

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Sooman, LindaBergqvist, MichaelGullbo, JoachimWu, XupingBlomquist, ErikLennartsson, Johan

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