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Therapeutic implica...
Therapeutic implications for the induced levels of Chk1 in Myc- expressing cancer cells
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- Höglund, Andreas, 1980- (author)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Jonas Nilsson
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- Nilsson, Lisa M, 1976 (author)
- Gothenburg University,Göteborgs universitet,Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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- Muralidharan, Somsundar Veppil (author)
- Gothenburg University,Göteborgs universitet,Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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Hasvold, Lisa A. (author)
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Merta, Philip (author)
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Rudelius, Martina (author)
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Nikolova, Viktoriya (author)
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Keller, Ulrich (author)
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- Nilsson, Jonas A. (author)
- Gothenburg University,Göteborgs universitet,Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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(creator_code:org_t)
- Philadelphia : Association for Cancer Research, 2011
- 2011
- English.
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In: Clinical Cancer Research. - Philadelphia : Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:22, s. 7067-7079
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Purpose: The transcription factor c-Myc (or "Myc") is a master regulator of pathways driving cell growth and proliferation. MYC is deregulated in many human cancers, making its downstream target genes attractive candidates for drug development. We report the unexpected finding that B-cell lymphomas from mice and patients exhibit a striking correlation between high levels of Myc and checkpoint kinase 1 (Chk1). Experimental Design: By in vitro cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of Chk1 in Myc-overexpressing cells. Results: We show that Myc indirectly induces Chek1 transcript and protein expression, independently of DNA damage response proteins such as ATM and p53. Importantly, we show that inhibition of Chk1, by either RNA interference or a novel highly selective small molecule inhibitor, results in caspase-dependent apoptosis that affects Myc-overexpressing cells in both in vitro and in vivo mouse models of B-cell lymphoma. Conclusion: Our data suggest that Chk1 inhibitors should be further evaluated as potential drugs against Myc-driven malignancies such as certain B-cell lymphoma/leukemia, neuroblastoma, and some breast and lung cancers. Clin Cancer Res; 17(22); 7067-79. (C) 2011 AACR.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Myc
- Chk1
- Molecular biology
- Molekylärbiologi
- molekylärbiologi
- Molecular Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Höglund, Andreas ...
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Nilsson, Lisa M, ...
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Muralidharan, So ...
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Hasvold, Lisa A.
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Merta, Philip
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Rudelius, Martin ...
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Nikolova, Viktor ...
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Keller, Ulrich
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Nilsson, Jonas A ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Clinical Cancer ...
- By the university
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Umeå University
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University of Gothenburg