Identification of differentially expressed genes following treatment of monkey kidney cells with the mycotoxin fumonisin B1

Fumonisin B1 (FB1) is a mycotoxin produced by the phytopathogenic fungus Fusarium moniliforme, which structurally resembles sphingoid bases. FB1 perturbs sphingolipid synthesis by inhibiting the activity of ceramide synthase. Depending on the host, ingestion of FB1 causes equine leukoencephalomalacia or porcine pulmonary edema. It is also carcinogenic to rats and may play a role in certain human cancers. Previous studies showed that FB1 repressed specific isoforms of protein kinase C and cyclin-dependent kinase 2 (CDK2) activity. Conversely, FB1 induced expression of CDK inhibitors, p21Waf1/Cip1, p27Kip1, and p57Kip2 in monkey kidney cells (CV-1). Consequently, FB1 treatment of CV-1 cells leads to cell-cycle arrest and apoptosis. The baculovirus IAP gene (inhibitor of apoptosis), which blocks tumor necrosis factor (TNF)-induced apoptosis, protects several fibroblast cell types from apoptosis, suggesting the TNF pathway is important for FB1-induced apoptosis. To identify genes that are induced by FB1, we used a PCR-based subtraction approach. Eight genes that showed high similarity (> 90%) to known mammalian genes were identified. These genes included: tumor necrosis factor type 1 receptor associated protein 2 (TRAP2), human leukemia virus receptor (GLVR1), human Scaffold attachment factor A (SAF-A) also called heterogeneous nuclear ribonucleoprotein U (hnRNP-U), human protein kinase C-binding protein (RACK7), human oligosaccharyl transferase STT3 subunit, mouse WW-domain binding protein 2 (WBP2), human fibronectin, and an unknown human clone. The ability of FB1 to alter gene expression and signal transduction pathways may be necessary for its carcinogenic and toxic effects.