| Hedgehog signaling in glioblastoma multiforme. | |
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MedLine Citation:
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PMID: 22406999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults with a median survival of 14.6 mo under the best available treatment. New treatment strategies are therefore urgently required, for which a profound understanding of tumor biology is necessary. Much effort has been devoted to tumor-specific aberrant signaling processes. Recently it was discovered that the transcription factor Gli1, which is activated by hedgehog signaling, is a highly predictive marker in GBM, as determined by immunohistochemistry. To determine whether GBM cells have transcriptionally active Gli1, we performed experiments with reporter genes with cells isolated from surgically removed human tumors and cell lines. We also determined whether the hedgehog signaling inhibitor cyclopamine influences reporter gene expression and cell viability, and we determined the expression of Gli1, SHH and Patched1 by quantitative real-time RT-PCR. Reporter gene analysis of nine cultures and four cell lines demonstrated a significantly enhanced transcriptional activity in six tumor cell cultures and all cell lines. Analysis of cell viability in the presence of cyclopamine revealed a response of all cell cultures with the exception of one primary culture and one cell line, but only one cell line responded to cyclopamine with reduced hedgehog signaling activity. This indicates that the toxicity of cyclopamine toward GBM cells is independent from hedgehog signaling. Since no correlation between hedgehog activity and SHH, Gli1 and Patched1 mRNA levels was observed we conclude that other mechanisms aside from transcriptional regulation of these factors are responsible for hedgehog activity in tumor cells derived from GBM. |
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Authors:
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Stefanie Braun; Henry Oppermann; Antje Mueller; Christof Renner; Amalya Hovhannisyan; Rainer Baran-Schmidt; Rolf Gebhardt; Alan Hipkiss; Joachim Thiery; Jürgen Meixensberger; Frank Gaunitz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-05-01 |
Journal Detail:
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Title: Cancer biology & therapy Volume: 13 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-07-19 Completed Date: 2012-12-14 Revised Date: 2013-02-05 |
Medline Journal Info:
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Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 487-95 Citation Subset: IM |
Affiliation:
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Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig AöR, Leipzig, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cell Survival / drug effects Gene Expression Regulation, Neoplastic Genes, Reporter Glioblastoma / metabolism* Hedgehog Proteins / metabolism* Humans Oncogene Proteins / genetics, metabolism Receptors, Cell Surface / genetics Signal Transduction* Trans-Activators / genetics, metabolism Transcription, Genetic Transfection Veratrum Alkaloids / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Gli protein; 0/Hedgehog Proteins; 0/Oncogene Proteins; 0/Receptors, Cell Surface; 0/Trans-Activators; 0/Veratrum Alkaloids; 0/patched receptors; ZH658AJ192/cyclopamine |
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