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Differential expression of genes during aflatoxin B(1)-induced hepatocarcinogenesis in tree shrews.

ABSTRACT: AIM:Through exploring the regulation of gene expression during hepatocarcinogenesis induced by aflatoxin B(1) (AFB(1)), to find out the responsible genes for hepatocellular carcinoma (HCC) and to further understand the underlying molecular mechanism. METHODS:Tree shrews (Tupaia belangeri chinensis) were treated with or without AFB(1) for about 90 weeks. Liver biopsies were performed regularly during the animal experiment. Eight shares of total RNA were respectively isolated from 2 HCC tissues, 2 HCC-surrounding non-cancerous liver tissues, 2 biopsied tissues at the early stage (30th week) of the experiment from the same animals as above, 1 mixed sample of three liver tissues biopsied at the beginning (0th week) of the experiment, and another 1 mixed sample of two liver tissues from the untreated control animals biopsied at the 90th week of the experiment. The samples were then tested with the method of Atlas(TM) cDNA microarray assay. The levels of gene expression in these tissues taken at different time points during hepatocarcinogenesis were compared. RESULTS:The profiles of differently expressed genes were quite different in different ways of comparison. At the same period of hepatocarcinogenesis, the genes in the same function group usually had the same tendency for up- or down-regulation. Among the checked 588 genes that were known to be related to human cancer, 89 genes (15.1%) were recognized as "important genes" because they showed frequent changes in different ways of comparison. The differentially expressed genes during hepatocarcinogenesis could be classified into four categories: genes up-regulated in HCC tissue, genes with similar expressing levels in both HCC and HCC-surrounding liver tissues which were higher than that in the tissues prior to the development of HCC, genes down-regulated in HCC tissue, and genes up-regulated prior to the development of HCC but down-regulated after the development of HCC. CONCLUSION:A considerable number of genes could change their expressing levels both in HCC and in HCC-surrounding non-cancerous liver tissues. A few modular genes were up-regulated only in HCC but not in surrounding liver tissues, while some apoptosis-related genes were down-regulated in HCC and up-regulated in surrounding liver tissues. To compare gene-expressing levels among the liver tissues taken at different time points during hepatocarcinogenesis may be helpful to locate the responsible gene (s) and understand the mechanism for AFB(1) induced liver cancer.

SUBMITTER: Li Y

PROVIDER: S-EPMC4716968 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature

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Differential expression of genes during aflatoxin B(1)-induced hepatocarcinogenesis in tree shrews.

Li Yuan Y Wan Da-Fang DF Su Jian-Jia JJ Cao Ji J Ou Chao C Qiu Xiao-Kun XK Ban Ke-Chen KC Yang Chun C Qin Liu-Liang LL Luo Dan D Yue Hui-Fen HF Zhang Li-Sheng LS Gu Jian-Ren JR

World journal of gastroenterology 20040201 4

<h4>Aim</h4>Through exploring the regulation of gene expression during hepatocarcinogenesis induced by aflatoxin B(1) (AFB(1)), to find out the responsible genes for hepatocellular carcinoma (HCC) and to further understand the underlying molecular mechanism.<h4>Methods</h4>Tree shrews (Tupaia belangeri chinensis) were treated with or without AFB(1) for about 90 weeks. Liver biopsies were performed regularly during the animal experiment. Eight shares of total RNA were respectively isolated from 2 ...[more]

PMID: 14966905

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Project description:PurposeThe tree shrew model of refractive development is particularly useful because, like humans, tree shrews have a fibrous sclera. Selective changes in some candidate extracellular matrix proteins and mRNAs have been found in the sclera during the development of and recovery from induced myopia. We undertook a more neutral proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry to identify scleral proteins that are differentially expressed during the development of and recovery from lens-induced myopia.MethodsFive tree shrews (Tupaia glis belangeri) wore a monocular -5 D lens for four days, starting 24 days after natural eye opening. At the end of this time, all treated eyes had partially compensated for the lens and were -3.5+/-0.7 D (mean+/-SEM) myopic relative to the untreated fellow control eyes. An additional five animals wore a -5 D lens for 11-13 days followed by four days of recovery without the -5 D lens. The amount of recovery was 1.6+/-0.4 D. Scleral proteins from both groups were then isolated and resolved by two-dimensional gel electrophoresis and spots that were differentially expressed were identified by mass spectrometry.ResultsThe scleral protein profile typically displayed about 700 distinct protein spots within the pH 5-8 range. Comparison of the treated-eye and control-eye scleras of the lens-compensation animals revealed five spots that were significantly and differentially expressed in all five pairs of eyes; all were downregulated 1.2 to 1.7 fold in the treated eye. These proteins were identified as: pigment epithelium-derived factor (PEDF), procollagen Ialpha, procollagen Ialpha2, and thrombospondin I (two spots). In the recovering eyes, the two thrombospondin I spots remained lower in abundance while PEDF and the procollagens were no longer downregulated. In addition, 78 kDa glucose-regulated protein (GRP 78), a member of the heat shock protein 70 family, was slightly upregulated 1.3 fold.ConclusionsWe found consistent results across animals that were of a magnitude consistent with the physiologically small changes to the focal plane of these eyes. Changes in collagen confirm previous findings, but downregulation of thrombospondin I adds detail to our understanding of the chain of signals that regulates scleral creep rate. The differential changes in PEDF and GRP 78 were not expected based on previous studies and demonstrate the utility of the proteomic approach in tree shrew sclera.

Dataset Information

Differential expression of genes during aflatoxin B(1)-induced hepatocarcinogenesis in tree shrews.

Publications

Differential expression of genes during aflatoxin B(1)-induced hepatocarcinogenesis in tree shrews.

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