Genomics

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Gene expression in trout hepatocellular carcinoma


ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and its occurrence is associated with a number of environmental factors including ingestion of the dietary contaminant aflatoxin B1 (AFB1). While etiology of the disease is relatively well defined, the molecular mechanisms of tumorigenesis are poorly understood. In this study, we examined, for the first time, gene expression of AFB1-induced HCC by microarray in the rainbow trout (Oncorhynchus mykiss) tumor model. Carcinogenesis was initiated in trout embryos with 50 ppb AFB1 and 13 months later control livers, tumors and tumor-adjacent liver tissues were isolated from juvenile fish. Global gene expression was determined in histologically confirmed HCCs compared to non-cancerous adjacent tissue and sham-initiated control liver utilizing a rainbow trout oligonucleotide array containing approximately 1500 genes of known or probable relevance to toxicology, comparative immunology, carcinogenesis and stress physiology. We observed distinct gene regulation patterns in HCC compared to non-cancerous tissue including upregulation of genes important for cell cycle control, transcription, cytoskeletal formation and the acute phase response and down regulation of genes involved in drug metabolism, lipid metabolism and retinol metabolism. These gene classes have previously been observed to be important in the regulation of HCC in human and rodent models. Overall, these findings contribute to a better understanding of the mechanism of AFB1-induced hepatocarcinogenesis in the trout model and identify conserved genes important for carcinogenesis in species separated evolutionarily by more than 400 million years. Keywords: other

ORGANISM(S): Oncorhynchus mykiss

PROVIDER: GSE2686 | GEO | 2005/09/06

SECONDARY ACCESSION(S): PRJNA92191

REPOSITORIES: GEO

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