Identification of proteins regulated by interferon‐α in resistant and sensitive malignant melanoma cell lines

Abstract

Treatment of patients with malignant melanoma with interferon‐α achieves a response in a small but significant subset of patients. Currently, although much is known about interferon biology, little is known about either the particular mechanisms of interferon‐α activity that are crucial for response or why only some patients respond to interferon‐α therapy. Two melanoma cell lines (MeWo and MM418) that are known to differ in their response to the antiproliferative activity of interferon‐α, have been used as a model system to investigate interferon‐α action. Using a proteomics approach based on two‐dimensional polyacrylamide gel electrophoresis and mass spectrometry, several proteins induced in response to interferon‐α have been identified. These include a number of gene products previously known to be type I interferon responsive (tryptophanyl tRNA synthetase, leucine aminopeptidase, ubiquitin cross‐reactive protein, gelsolin, FUSE binding protein 2 and hPNPase) as well as a number of proteins not previously reported to be induced by type I interferon (cathepsin B, proteasomal activator 28α and α‐SNAP). Although the proteins upregulated by interferon‐α were common between the cell lines when examined at the level of Western blotting, the disparity in the basal level of cathepsin B was striking, raising the possibility that the higher level in MM418 may contribute to the sensitivity of this cell line to interferon‐α treatment.