Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The role of a novel CAR-induced gene TUBA8 in hepatocellular carcinoma cell lines

ABSTRACT: The Tuba8 gene was identified as a CAR-regulated gene that was induced during phenobarbital (PB) promotion of liver tumor. TUBA8 was then over-expressed in heaptocarcinoma cells to determine the function of TUBA8. First, identify genes that are regulated by CAR and are induced during liver tumor development. Second, overexpressiong of an identified gene in transformed cells to detemine the biolgical function of the gene product. In this manuscript, the TUBA8 gene was examined.

ORGANISM(S): Mus musculus

SUBMITTER: NIEHS Microarray Core

PROVIDER: E-GEOD-29108 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma cell lines.

Kamino Hiroki H Moore Rick R Negishi Masahiko M

Cancer genetics 20110701 7

Phenobarbital (PB), a nongenotoxic carcinogen, activates the nuclear constitutive active/androstane receptor (CAR), resulting in the transcriptional induction or repression of various hepatic genes. We previously demonstrated that liver tumors developed after chronic PB treatment only when CAR is present. To understand the molecular mechanism of tumor promotion, cDNA microarray analysis was performed. We identified tubulin alpha 8 (TUBA8) as one of the candidate genes that may be involved in liv ...[more]

PMID: 21872825

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Project description:Liver tumors in rodents are frequently induced by non-genotoxic carcinogens. These hepatocarcinogens generally activate hepatic nuclear receptors (e.g., CAR and PXR), resulting in a cascade of signals causing modifications in the expression of genes responsible for several processes involved in carcinogenesis. Evaluation of the carcinogenic potential of chemicals is a regulatory requirement but is time-consuming and expensive. Consequently, several short-term in vivo and in vitro approaches, using molecular tools, have been proposed as predictive models for non-genotoxic hepatocarcinogens. The objective of our study was to discriminate between chemicals that are either non-genotoxic hepatocarcinogens or merely hepatotoxicants and also between CAR and PXR modulators on the basis of their gene expression profiles. Thus, we treated rats for seven days with the hepatoxicants, diclofenac and diazepam, or with several CAR and PXR modulators, which were mainly hepatocarcinogens. Different hepatic gene expression profiles were obtained not only between the hepatotoxicants and the non-genotoxic hepatocarcinogens but also between the CAR activators phenobarbital, phenytoin and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene which were grouped together, and the two PXR activators pregnenolone 16Î±-carbonitrile and clotrimazole. Diethylstilbestrol had an expression profile that was quite distinct from the other PXR activators, suggesting that this compound is certainly not a classic PXR modulator. Moreover, some differences were observed between phenytoin (not considered as a hepatocarcinogen), and the other two CAR activators. Our data therefore indicate that discrimination is possible between hepatocarcinogens and hepatotoxicants, between CAR and PXR modulators and also between compounds within the same class of modulators using a short-term transcriptomic approach. CAR or PXR inducers were administered in suspension to rats (7 weeks old at start of treatment) by oral gavage at a daily dose for 7 consecutive days. Treatment-related changes in gene expression were determined in the liver using whole genome oligonucleotide microarrays.

Dataset Information

The role of a novel CAR-induced gene TUBA8 in hepatocellular carcinoma cell lines

Publications

Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma cell lines.

Similar Datasets

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