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c-Myc is able to sensitize human melanoma cells to diverse apoptotic triggers.

Peltenburg, LTC; de Bruin, EC; Meersma, D; Wilting, S; Jürgensmeier, JM; Schrier, PI; (2004) c-Myc is able to sensitize human melanoma cells to diverse apoptotic triggers. Melanoma Res , 14 (1) pp. 3-12.

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Abstract

Compared with other types of tumours, malignant melanomas are highly refractory to radio- or chemotherapy. To support the search for possible sensitizers, we explored the effects of the cellular oncoproteins c-Myc and N-Ras, which can decrease the clonogenic potential of irradiated p53-negative IGR39D melanoma cells. Using stable transfectants of this cell line, we showed that mutant N-Ras decreased the proliferation rate by inducing a prolonged cell cycle arrest. In contrast, c-Myc made these melanoma cells more prone to radiation-induced cell death. Membrane blebbing, the formation of apoptotic bodies and caspase activation, as measured by cleavage of Asp-Glu-Val-Asp (DEVD) substrate and poly(ADP-ribose) polymerase (PARP), indicate that these cells die by an apoptotic process. c-Myc also sensitized these p53-deficient melanoma cells to treatment with various cytotoxic drugs and heat shock. Similar results were obtained in inducible c-Myc models of IGR39D and in another melanoma cell line, 9007, which expresses functional p53. Together, these findings indicate that c-Myc is capable of sensitizing typically resistant tumour cells and that this occurs irrespective of the functional status of the p53 protein. Our results should facilitate the identification of factors that can be exploited for the treatment of aggressive cancers.

Type: Article
Title: c-Myc is able to sensitize human melanoma cells to diverse apoptotic triggers.
Location: England
Keywords: Apoptosis, Blotting, Western, Caspases, Cell Division, Enzyme Activation, Gamma Rays, Genes, ras, Humans, Melanoma, Poly(ADP-ribose) Polymerases, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-myc, Radiation Tolerance, Skin Neoplasms, Stress, Physiological, Tumor Cells, Cultured
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/1424492
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