| Mirk/Dyrk1B maintains the viability of quiescent pancreatic cancer cells by reducing levels of reactive oxygen species. | |
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MedLine Citation:
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PMID: 19351855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The kinase Mirk/dyrk1B mediated the clonogenic growth of pancreatic cancer cells in earlier studies. It is now shown that Mirk levels increased 7-fold in SU86.86 pancreatic cancer cells when over a third of the cells were accumulated in a quiescent G(0) state, defined by Hoechst/Pyronin Y staining. Depletion of Mirk by a doxycycline-inducible short hairpin RNA increased the G(0) fraction to approximately 50%, suggesting that Mirk provided some function in G(0). Mirk reduced the levels of reactive oxygen species (ROS) in quiescent cultures of SU86.86 cells and of Panc1 cells by increasing transcription of the antioxidant genes ferroxidase, superoxide dismutase (SOD)2, and SOD3. These genes were functional antioxidant genes in pancreatic cancer cells because ectopic expression of SOD2 and ferroxidase in Mirk-depleted cells lowered ROS levels. Quiescent pancreatic cancer cells quickly lost viability when depleted of Mirk because of elevated ROS levels, exhibiting up to 4-fold less colony-forming activity and 4-fold less capability for dye exclusion. As a result, reduction of ROS by N-acetyl cysteine led to more viable cells. Mirk also destabilizated cyclin D1 and D3 in quiescent cells. Thus, quiescent pancreatic cancer cells depleted of Mirk became less viable because they were damaged by ROS, and had increased levels of G(1) cyclins to prime cells to escape quiescence. |
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Authors:
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Xiaobing Deng; Daina Z Ewton; Eileen Friedman |
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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 Date: 2009-04-07 |
Journal Detail:
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Title: Cancer research Volume: 69 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-16 Completed Date: 2009-06-19 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 3317-24 Citation Subset: IM |
Affiliation:
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Pathology Department, Upstate Medical University, State University of New York, Syracuse, New York 13210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Survival
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physiology Cyclin D Cyclins / metabolism G0 Phase / physiology G1 Phase / physiology Humans Pancreatic Neoplasms / enzymology, genetics, metabolism*, pathology* Protein-Serine-Threonine Kinases / genetics, metabolism* Protein-Tyrosine Kinases / genetics, metabolism* RNA Interference Reactive Oxygen Species / metabolism* Superoxide Dismutase / biosynthesis, genetics, metabolism Transcription, Genetic Transfection Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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2R01CA67405/CA/NCI NIH HHS; R01 CA067405-09/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclin D; 0/Cyclins; 0/Reactive Oxygen Species; EC 1.15.1.1/SOD3 protein, human; EC 1.15.1.1/Superoxide Dismutase; EC 1.15.1.1/superoxide dismutase 2; EC 2.7.1.-/Dyrk kinase; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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