Exposure to aflatoxins is strongly associated with hepatocellular carcinoma (HCC). Hepatic progenitor cells have been suggested to participate in the development of HCC. To further explore the molecular basis of aflatoxin-induced carcinogenesis, we utilized transcriptome profiles to examine the global gene expression alterations of malignant transformed rat hepatic stem-like cells. WB-F344 cells were treated with continuous exposure to AFB1 (0.03, 0.1 and 0.2μM), and gained certain characteristics of transformed cells identified by soft agar assay. Microarray analyses of the transformed cells found that 785, 625, and 751 differentially expressed genes were detected in each exposure group, respectively. Hierarchical Clustering revealed that the effect of 0.1 and 0.2μM exposure on the cells was conformable. Importantly, Gene Ontology analysis showed that malignant transformation of the hepatic stem-like cells was closely correlated to biological process, related to cell motion, cell adhesion, immune response and signal transduction. Accordingly, biological pathways was focused mainly on focal adhesion, regulation of actin cytoskeleton, ECM-receptor interaction, MAPK, TGF-β and chemokine signaling pathway. A few genes involved in these pathways exhibited a dose response, including Cav2, Itgb3, Ccl2, Cx3cl1, Pdgfrb and Tmsb4x. These findings would contribute to a growing knowledgebase on the mechanism of aflatoxin-induced hepatocarcinogenesis.
Keywords: Aflatoxin B1, hepatic progenitor cells, transcriptome profiles, malignant transformation.