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Impaired Pten Expression in Human Malignant Peripheral Nerve Sheath Tumours
DC Field | Value | Language |
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dc.contributor.author | Bradtmoeller, Maren | - |
dc.contributor.author | Hartmann, Christian | - |
dc.contributor.author | Zietsch, Jan | - |
dc.contributor.author | Jaeschke, Sebastian | - |
dc.contributor.author | Mautner, Victor-F | - |
dc.contributor.author | Kurtz, Andreas | - |
dc.contributor.author | Park, Su-Jin | - |
dc.contributor.author | Baier, Michael | - |
dc.contributor.author | Harder, Anja | - |
dc.contributor.author | Reuss, David | - |
dc.contributor.author | von Deimling, Andreas | - |
dc.contributor.author | Heppner, Frank L. | - |
dc.contributor.author | Holtkamp, Nikola | - |
dc.date.accessioned | 2023-05-10T01:25:48Z | - |
dc.date.available | 2023-05-10T01:25:48Z | - |
dc.date.created | 2021-05-06 | - |
dc.date.issued | 2012-11 | - |
dc.identifier.citation | PLoS ONE, Vol.7 No.11 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://hdl.handle.net/10371/192324 | - |
dc.description.abstract | Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that develop in about 10% of patients with the genetic disease neurofibromatosis type 1 (NF1). Molecular alterations contributing to MPNST formation have only partially been resolved. Here we examined the role of Pten, a key regulator of the Pi3k/Akt/mTOR pathway, in human MPNST and benign neurofibromas. Immunohistochemistry showed that Pten expression was significantly lower in MPNST (n = 16) than in neurofibromas (n = 16) and normal nervous tissue. To elucidate potential mechanisms for Pten down-regulation or Akt/mTOR activation in MPNST we performed further experiments. Mutation analysis revealed absence of somatic mutations in PTEN (n = 31) and PIK3CA (n = 38). However, we found frequent PTEN promotor methylation in primary MPNST (11/26) and MPNST cell lines (7/8) but not in benign nerve sheath tumours. PTEN methylation was significantly associated with early metastasis. Moreover, we detected an inverse correlation of Pten-regulating miR-21 and Pten protein levels in MPNST cell lines. The examination of NF1-/- and NF1+/+ Schwann cells and fibroblasts showed that Pten expression is not regulated by NF1. To determine the significance of Pten status for treatment with the mTOR inhibitor rapamycin we treated 5 MPNST cell lines with rapamycin. All cell lines were sensitive to rapamycin without a significant correlation to Pten levels. When rapamycin was combined with simvastatin a synergistic anti-proliferative effect was achieved. Taken together we show frequent loss/reduction of Pten expression in MPNST and provide evidence for the involvement of multiple Pten regulating mechanisms. | - |
dc.language | 영어 | - |
dc.publisher | Public Library of Science | - |
dc.title | Impaired Pten Expression in Human Malignant Peripheral Nerve Sheath Tumours | - |
dc.type | Article | - |
dc.identifier.doi | 10.1371/journal.pone.0047595 | - |
dc.citation.journaltitle | PLoS ONE | - |
dc.identifier.wosid | 000311315300010 | - |
dc.identifier.scopusid | 2-s2.0-84876442920 | - |
dc.citation.number | 11 | - |
dc.citation.volume | 7 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kurtz, Andreas | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | LHERMITTE-DUCLOS-DISEASE | - |
dc.subject.keywordPlus | SUPPRESSOR GENE | - |
dc.subject.keywordPlus | NEUROFIBROMATOSIS TYPE-1 | - |
dc.subject.keywordPlus | MAMMALIAN TARGET | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | SOMA SIZE | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | MUTATION | - |
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