Novel Growth and Death Related Interferon-Stimulated Genes (ISGs) in Melanoma: Greater Potency of IFN-β Compared with IFN-α2

Interferon (IFN)-dependent cellular effects are mediated by transcriptional induction of responsive genes, collectively referred to as IFN-stimulated genes (ISGs). Which ISGs regulate the potent antiviral, antiproliferative, apoptosis-inducing, antiangiogenic, and immunologic effects of IFNs remains largely undetermined. To identify genes that might be useful for predicting or targeting apoptosis induction in response to IFNs, WM9 melanoma cells were assessed. WM9 cells had equivalent antiviral activity in response to IFN-β and IFN-α2 but underwent apoptosis only in response to IFN-β. RNA samples from WM9 cells and WM35 cells, a second melanoma cell line, treated with IFN-α2 or IFN-β were assessed on oligonucleotide arrays. For 95% of genes assessed, IFN-β was more potent than IFN-α2 in inducing ISG expression. Using a 22,000-gene oligonucleotide array, the largest yet reported for assessing ISG induction, approximately 910 genes were identified as induced by IFN-β at 500 U/ml, and 260 ISGs were identifie...