| Suppression of the mouse double minute 4 gene causes changes in cell cycle control in a human mesothelial cell line responsive to ultraviolet radiation exposure. | |
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MedLine Citation:
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PMID: 19472317 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The TP53 tumor suppressor gene is the most frequently inactivated gene in human cancer identified to date. However, TP53 mutations are rare in human mesotheliomas, as well as in many other types of cancer, suggesting that aberrant TP53 function may be due to alterations in its regulatory pathways. Mouse double minute 4 (MDM4) has been shown to be a key regulator of TP53 activity, both independently as well as in concert with its structural homolog, Mouse Double Minute 2 (MDM2). The purpose of this study was to characterize the effects of MDM4 suppression on TP53 and other proteins involved in cell cycle control before and after ultraviolet (UV) exposure in MeT5a cells, a nonmalignant human mesothelial line. Short hairpin RNA (shRNA) was used to investigate the impact of MDM4 on TP53 function and cellular transcription. Suppression of MDM4 was confirmed by Western blot. MDM4 suppressed cells were analyzed for cell cycle changes with and without exposure to UV. Changes in cell growth as well as differences in the regulation of direct transcriptional targets of TP53, CDKN1A (cyclin-dependent kinase 1alpha, p21) and BAX, suggest a shift from cell cycle arrest to apoptosis upon increasing UV exposure. These results demonstrate the importance of MDM4in cell cycle regulation as well as a possible role inthe pathogenesis of mesothelioma-type cancers. |
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Authors:
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Melisa Bunderson-Schelvan; Amy K Erbe; Corbin Schwanke; Mark A Pershouse |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Environmental and molecular mutagenesis Volume: 50 ISSN: 1098-2280 ISO Abbreviation: Environ. Mol. Mutagen. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-07 Completed Date: 2009-12-15 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 8800109 Medline TA: Environ Mol Mutagen Country: United States |
Other Details:
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Languages: eng Pagination: 753-9 Citation Subset: IM |
Affiliation:
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The University of Montana, Center for Environmental Health Sciences, Missoula, Montana, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / genetics Cell Cycle / genetics* Cell Line Epithelium / radiation effects* Gene Silencing* Genes, p53 Humans Mice Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins / genetics* Ubiquitin-Protein Ligases / genetics* Ultraviolet Rays* |
| Grant Support | |
ID/Acronym/Agency:
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P20 RR017670-010005/RR/NCRR NIH HHS; RR017670/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Mdm4 protein, mouse; 0/Proto-Oncogene Proteins; EC 6.3.2.19/Ubiquitin-Protein Ligases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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