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Targeting ornithine...
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Nilsson, Jonas AUmeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Nilsson
(author)
Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation.
- Article/chapterEnglish2005
Publisher, publication year, extent ...
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-16704
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-16704URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Checkpoints that control Myc-mediated proliferation and apoptosis are bypassed during tumorigenesis. Genes encoding polyamine biosynthetic enzymes are overexpressed in B cells from E mu-Myc transgenic mice. Here, we report that disabling one of these Myc targets, Ornithine decarboxylase (Odc), abolishes Myc-induced suppression of the Cdk inhibitors p21(Cip1) and p27(Kip1), thereby impairing Myc's proliferative, but not apoptotic, response. Moreover, lymphoma development was markedly delayed in E mu-Myc;Odc(+/-) transgenic mice and in E mu-Myc mice treated with the Odc inhibitor difluoromethylornithine (DFMO). Strikingly, tumors ultimately arising in E mu-Myc;Odc(+/-) transgenics lacked deletions of Arf, suggesting that targeting Odc forces other routes of transformation. Therefore, Odc is a critical Myc transcription target that regulates checkpoints that guard against tumorigenesis and is an effective target for cancer chemoprevention.
Subject headings and genre
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Animals
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Apoptosis/drug effects
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B-Lymphocytes/chemistry/drug effects/metabolism
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Cell Cycle Proteins/genetics/metabolism
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Cell Proliferation/drug effects
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Eflornithine/pharmacology
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Gene Expression/drug effects
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Gene Expression Regulation; Neoplastic/drug effects
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Heterozygote
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Lymphoma/drug therapy/genetics/*metabolism
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Mice
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Mice; Inbred C57BL
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Mice; Knockout
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Mice; Mutant Strains
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Mice; Transgenic
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Organ Size/drug effects
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Ornithine Decarboxylase/antagonists & inhibitors/genetics/*metabolism
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Polyamines/metabolism
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Proto-Oncogene Proteins c-myc/genetics/*metabolism
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Spleen/pathology
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Survival Rate
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Tumor Suppressor Protein p14ARF/genetics/metabolism
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Tumor Suppressor Proteins/genetics/metabolism
Added entries (persons, corporate bodies, meetings, titles ...)
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Keller, Ulrich B
(author)
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Baudino, Troy A
(author)
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Yang, Chunying
(author)
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Norton, Sara
(author)
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Old, Jennifer A
(author)
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Nilsson, Lisa MUmeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Heby
(author)
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Neale, Geoffrey
(author)
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Kramer, Debora L
(author)
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Porter, Carl W
(author)
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Cleveland, John L
(author)
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Umeå universitetInstitutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
(creator_code:org_t)
Related titles
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In:Cancer Cell7:5, s. 433-441535-6108
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To the university's database
- By the author/editor
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Nilsson, Jonas A
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Keller, Ulrich B
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Baudino, Troy A
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Yang, Chunying
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Norton, Sara
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Old, Jennifer A
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show more...
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Nilsson, Lisa M
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Neale, Geoffrey
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Kramer, Debora L
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Porter, Carl W
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Cleveland, John ...
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- Articles in the publication
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Cancer Cell
- By the university
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Umeå University