title: 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-beta) 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 Temporally Spaced Subtracted (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-gamma, 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-beta) + MEZ, can elicit signaling pathways and gene expression changes also regulated by type II immune interferon.
authors.affiliation: Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lin
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: P B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001483:Base Sequence; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004273:DNA, Neoplasm; D004224:Diterpenes; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011994:Recombinant Proteins; D053676:Syntenins; D013729:Terpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004224:Diterpenes; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C109621:SDCBP protein, human; D053676:Syntenins; D013729:Terpenes; C011309:mezerein; D007371:Interferon-gamma