| IQGAP1 and vimentin are key regulator genes in naturally occurring hepatotumorigenesis induced by oxidative stress. | |
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MedLine Citation:
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PMID: 20015863 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To identify key genes involved in the complex multistep process of hepatotumorigenesis, we reduced multivariate clinicopathological variables by using the Long-Evans Cinnamon rat, a model with naturally occurring and oxidative stress-induced hepatotumorigenesis. Gene expression patterns were analyzed serially by profiling liver tissues from rats of a naive status (4 weeks old), through to those with chronic hepatitis (26 and 39 weeks old) to tumor development (67 weeks old). Of 31 099 probe sets used for microarray analysis, 87 were identified as being upregulated in a stepwise manner during disease progression and tumor development. Quantitative real-time reverse transcription-polymerase chain reaction and statistical analyses verified that IQGAP1 and vimentin mRNA expression levels increased significantly throughout hepatotumorigenesis. A hierarchical clustering algorithm showed both genes clustered together and in the same cluster group. Immunohistochemical and western blot analyses showed similar increases in protein levels of IAGAP1 and vimentin. Finally, pathway analyses using text-mining technology with more comprehensive and recent gene-gene interaction data identified IQGAP1 and vimentin as important nodes in underlying gene regulatory networks. These findings enhance our understanding of the multistep hepatotumorigenesis and identification of target molecules for novel treatments. |
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Authors:
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Akihito Tsubota; Kenji Matsumoto; Kaoru Mogushi; Koichi Nariai; Yoshihisa Namiki; Sadayori Hoshina; Hiroshi Hano; Hiroshi Tanaka; Hirohisa Saito; Norio Tada |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-16 |
Journal Detail:
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Title: Carcinogenesis Volume: 31 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-05 Completed Date: 2010-04-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 504-11 Citation Subset: IM |
Affiliation:
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Institute of Clinical Medicine and Research, Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan. atsubo@jikei.ac.jp |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSM4343398; GSM4343401; GSM434390; GSM434391; GSM434392; GSM434393; GSM434394; GSM434395; GSM434397 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Copper / metabolism Disease Models, Animal Disease Progression Gene Expression Profiling Gene Regulatory Networks / genetics* Genetic Association Studies Hepatolenticular Degeneration Humans Liver / metabolism Liver Neoplasms, Experimental / etiology, genetics*, metabolism Male Molecular Sequence Data Oligonucleotide Array Sequence Analysis Oxidative Stress* Precancerous Conditions / genetics, metabolism RNA, Messenger / biosynthesis, genetics Rats Rats, Inbred LEC Rats, Long-Evans Reverse Transcriptase Polymerase Chain Reaction Vimentin / biosynthesis, genetics, physiology* ras GTPase-Activating Proteins / biosynthesis, genetics, physiology* |
| Chemical | |
Reg. No./Substance:
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0/IQ motif containing GTPase activating protein 1; 0/RNA, Messenger; 0/Vimentin; 0/ras GTPase-Activating Proteins; 7440-50-8/Copper |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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