ORIGINAL ARTICLE: PDF OnlyMutated N-ras upregulates Bcl-2 in human melanoma in vitro and in SCID miceBorner, C.; Wadl, H. Schlagbauer; Fellay, I.; Selzer, E.; Polterauer, P.; Jansen, B.Author Information Institute of Biochemistry, University of Fribourg, Rue du Musee 5, CH-1700 Fribourg, Switzerland (C. Borner, I. Fellay). Department of Dermatology, Division of General Dermatology (H. Schlagbauer Wadl, B. Jansen), Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology (H. Schlagbauer Wadl, B. Jansen), Department of Radiation Therapy (E. Selzer) and Department of Surgery, Division of Vascular Surgery (P. Polterauer), University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Melanoma Research: August 1999 - Volume 9 - Issue 4 - p 347-350 Buy Abstract Activation of the N-ras gene by point mutation occurs in about 15% of all human melanomas. In recently established severe combined immunodeficiency (SCID) mouse xenotransplantatlon models for human melanoma, we demonstrated that mutated N-ras not only contributes to tumour growth by enhancing cellular proliferation, but also by blocking apoptosis. Mutated N-ras overexpresslon protected human melanomas from naturally occurring apoptosis and, in a more pronounced way, from chemotherapy-induced apoptosis in vitro and in vivo. Given the potential clinical importance of these findings we sought to determine the underlying mechanism. We found that mutated N-ras specifically upregulates the expression of the anti-apoptosis gene bcl-2 in two human melanoma cell lines in vitro and in SCID mice. Neither the expression of the antiapoptotic protein Bcl-xL nor that of the pro-apoptotic proteins Bax and Bak were altered in cells expressing mutated N-Ras. The increase in Bcl-2 expression mediated by mutated ras therefore qualifies as a rational explanation for the enhanced chemoresistance of human melanoma expressing mutated N-Ras. © 1999 Lippincott Williams & Wilkins, Inc.