Activated N-ras contributes to the chemoresistance of human melanoma in severe combined immunodeficiency (SCID) mice by blocking apoptosis
Jansen, B.; Schlagbauer-Wadl, H.; Eichler, H.G.; Wolff, K.; van Elsas, A.; Schrier, P.I.; Pehamberger, H.
Cancer Research 57(3): 362-365
1997
ISSN/ISBN: 0008-5472 PMID: 9012455 Document Number: 470346
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.