| Induction of senescence in MYCN amplified neuroblastoma cell lines by hydroxyurea. | |
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MedLine Citation:
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PMID: 17106870 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recently, it was shown that MYCN amplified cells spontaneously expulse extrachromosomally amplified gene copies by micronuclei formation. Furthermore, it was shown that these cells lose their malignant phenotype and start to age. We tested whether it is possible to encourage neuroblastoma tumor cells to enter the senescence pathway by low concentrations of the micronuclei-inducing drug hydroxyurea (HU). We studied the effect of HU on 12 neuroblastoma cell lines with extra- or intrachromosomally amplified MYCN copies and without amplification. Two extrachromosomally amplified neuroblastoma cell lines (with double minutes) were investigated in detail. Already after 3 weeks of HU treatment, the BrdU uptake dropped to 25% of the starting cells. After 4 weeks, enlarged and flattened cells (F-cells) and increased granularity in the majority of cells were observed. A drastic reduction of the MYCN copy number-down to one copy per cell-associated with CD44 and MHCI upregulation in up to 100% of the HU treated neuroblastoma cells was found after 5-8 weeks. Telomere length was reduced to half the length within 8 weeks of HU treatment, and telomerase activity was not detectable at this time, while being strongly expressed at the beginning. All these features and the expression of senescence-associated-beta-galactosidase (SA-beta-GAL) in up to 100% of the cells support the hypothesis that these cells entered the senescence pathway. Thus, low-dose HU is a potent senescence elicitor for tumor cells with gene amplification, possibly representing an attractive additional strategy for treatment of this subset of tumors. |
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Authors:
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R Narath; I M Ambros; A Kowalska; E Bozsaky; P Boukamp; P F Ambros |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Genes, chromosomes & cancer Volume: 46 ISSN: 1045-2257 ISO Abbreviation: Genes Chromosomes Cancer Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2006-12-07 Completed Date: 2007-10-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9007329 Medline TA: Genes Chromosomes Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 130-42 Citation Subset: IM |
Copyright Information:
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Copyright 2006 Wiley-Liss, Inc. |
Affiliation:
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Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Vienna, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Cell Aging / drug effects*, genetics Cell Line, Tumor Gene Amplification / physiology* Humans Hydroxyurea / pharmacology* Neuroblastoma / drug therapy, genetics*, metabolism Nuclear Proteins / biosynthesis, genetics* Oncogene Proteins / biosynthesis, genetics* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/MYCN protein, human; 0/Nuclear Proteins; 0/Oncogene Proteins; 127-07-1/Hydroxyurea |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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