Document Detail


IQGAP1 and vimentin are key regulator genes in naturally occurring hepatotumorigenesis induced by oxidative stress.
MedLine Citation:
PMID:  20015863     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-16
Journal Detail:
Title:  Carcinogenesis     Volume:  31     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-05     Completed Date:  2010-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  504-11     Citation Subset:  IM    
Affiliation:
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.:
GEO/GSM4343398;  GSM4343401;  GSM434390;  GSM434391;  GSM434392;  GSM434393;  GSM434394;  GSM434395;  GSM434397
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MeSH Terms
Descriptor/Qualifier:
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:
0/IQ motif containing GTPase activating protein 1; 0/RNA, Messenger; 0/Vimentin; 0/ras GTPase-Activating Proteins; 7440-50-8/Copper

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