Activated N-Ras contributes to the chemoresistance of human melanoma in severe combined immunodeficiency (SCID) mice by blocking apoptosis

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 ac...

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Bibliographic Details
Published inCancer research (Chicago, Ill.) Vol. 57; no. 3; pp. 362 - 365
Main Authors JANSEN, B, SCHLAGBAUER-WADL, H, EICHLER, H.-G, WOLFF, K, VAN ELSAS, A, SCHRIER, P. I, PEHAMBERGER, H
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 01.02.1997
Subjects
Animals
Antineoplastic agents
Apoptosis - drug effects
Biological and medical sciences
Cisplatin - pharmacology
Drug Resistance
Female
General aspects
Genes, ras - physiology
Humans
Medical sciences
Melanoma - drug therapy
Melanoma - pathology
Mice
Mice, SCID
Pharmacology. Drug treatments
Point Mutation
Tumor Cells, Cultured
Antineoplastic agent
Human
Rodentia
Melanoma
Activation
In vitro
Cisplatin
Resistance
In vivo
Vertebrata
Mammalia
Mouse
Cell death
Animal
Established cell line
Point mutation
Tumor
Onc gene
Mechanism of action
Tumor cell
Apoptosis
Platinum II Complexes
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Summary: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.
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ISSN:0008-5472
1538-7445