Identification of differentially expressed genes following treatment of monkey kidney cells with the mycotoxin fumonisin B-1

Fumonisin B-1 (FB1) is a mycotoxin produced by the phytopathogenic fungus F usarium moniliforme, which structurally resembles sphingoid bases. FB1 pert urbs sphingolipid synthesis by inhibiting the activity of ceramide synthase . Depending on the host, ingestion of FB1 causes equine leukoencephalomalac ia or porcine pulmonary edema. It is also carcinogenic to rats and may play a role in certain human cancers. Previous studies showed that FB1 represse d specific isoforms of protein kinase C and cyclin-dependent kinase 2 (CDK2 ) activity. Conversely, FB1 induced expression of CDK inhibitors, p21(Waf1/ Cip1), p27(Kip1), and p57(Kip2) 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 fro m apoptosis, suggesting the TNF pathway is important for FB1-induced apopto sis. To identify genes that are induced by FB1, we used a PCR-based subtrac tion approach. Eight genes that showed high similarity (> 90%) to known mam malian genes were identified. These genes included: tumor necrosis factor t ype 1 receptor associated protein 2 (TRAP2), human leukemia virus receptor (GLVR1), human Scaffold attachment factor A (SAF-A) also called heterogeneo us nuclear ribonucleoprotein U (hnRNPU), human protein kinase C-binding pro tein (RACK7), human oligosaccharyl transferase STT3 subunit, mouse WW-domai n binding protein 2 (WBP2), human fibronectin, and an unknown human clone. The ability of FB1 to alter gene expression and signal transduction pathway s may be necessary for its carcinogenic and toxic effects. (C) 2001 Elsevie r Science Ltd. All rights reserved.