title: Activated N-ras contributes to the chemoresistance of human melanoma in severe combined immunodeficiency (SCID) mice by blocking apoptosis.
abstract: Activation of the N-ras gene by point mutations occurs in about 15 % of all human melanomas. Using recently established melanoma severe combined immunodeficiency-human mouse xenotransplantation models, here we further investigate the biological significance of these mutations. We demonstrate that activated N-ras significantly contributes to the chemoresistance of human melanoma both in vitro and in vivo by blocking apoptosis. Overexpression of wild-type N-ras had no such effects. With antisense oligonucleotides and farnesyltransferase inhibitors, tools capable of blocking Ras function on the therapeutic horizon, our observation that activated N-ras is not a bystander but a factor worth targeting to improve therapeutic outcome in melanoma gains additional importance.
authors.affiliation: Department of Clinical Pharmacology, Section of Experimental Oncology, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Jansen
authors.forename: H
authors.initials: H
authors.lastname: Schlagbauer-Wadl
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
authors.forename: K
authors.initials: K
authors.lastname: Wolff
authors.forename: A
authors.initials: A
authors.lastname: van Elsas
authors.forename: P I
authors.initials: PI
authors.lastname: Schrier
authors.forename: H
authors.initials: H
authors.lastname: Pehamberger
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D011905:Genes, ras / Q000502:physiology*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D017354:Point Mutation; D014407:Tumor Cells, Cultured
chemical_list: D002945:Cisplatin