Melanoma differentiation associated gene-9, mda-9, is a human gamma interferon responsive gene

Abstract

Subtraction hybridization using a cDNA library prepared from temporally spaced mRNAs from human melanoma cells treated with recombinant human fibroblast interferon (IFN- β) plus mezerein (MEZ) that induces terminal differentiation ( tester cDNA library) and a temporally spaced cDNA library prepared from actively proliferating melanoma cells ( driver cDNA library) produced a T emporally S paced S ubtracted ( TSS) cDNA library. This approach resulted in the identification of melanoma differentiation associated ( mda) genes displaying both enhanced and suppressed expression during growth inhibition and differentiation. In the present report, we describe a novel cDNA mda-9 that consists of 2084 nucleotides, and encodes a protein of 298 amino acids with a predicted M r of approx. 33 kDa. Treatment of human SV40-immortalized normal melanoma cells with immune interferon, INF- γ, induces growth suppression and enhances mda-9 expression without inducing terminal differentiation. These results establish that induction of terminal differentiation in human melanoma cells, using the combination of a type I interferon (IFN- β)+MEZ, can elicit signaling pathways and gene expression changes also regulated by type II immune interferon.