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Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines

Oncogene volume 23, pages 2347–2356 (2004)Cite this article

Abstract

We have conducted an analysis of genetic alterations in spontaneous murine melanoma cell line B16F0 and its two metastatic clones, B16F1 and B16F10 and the carcinogen-induced murine melanoma cell lines CM519, CM3205, and K1735. We found that unlike human melanomas, the murine melanoma cell lines did not have activating mutations in the Braf oncogene at exon 11 or 15. However, there were distinct patterns of alterations in the ras, Ink4a/Arf, and p53 genes in the two melanoma groups. In the spontaneous B16 melanoma cell lines, expression of p16Ink4a and p19Arf tumor suppressor proteins was lost as a consequence of a large deletion spanning Ink4a/Arf exons 1α, 1β, and 2. In contrast, the carcinogen-induced melanoma cell lines expressed p16Ink4a but had inactivating mutations in either p19Arf (K1735) or p53 (CM519 and CM3205). Inactivation of p19Arf or p53 in carcinogen-induced melanomas was accompanied by constitutive activation of mitogen-activated protein kinases (MAPKs) and/or mutation-associated activation of N-ras. These results indicate that genetic alterations in p16Ink4a/p19Arf, p53 and ras-MAPK pathways can cooperate in the development of murine melanoma.

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Acknowledgements

We thank Dr Maureen Goode for editing the manuscript. This work was supported by National Cancer Institute grant CA 46523 (to HNA), National Institute of Environmental Health Sciences Center Grant ES07784, and The University of Texas MD Anderson Cancer Center institutional core Grant CA 16672.

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  1. Department of Immunology, The University of Texas MD Anderson Cancer Center, Unit 902, PO Box 301402, Houston, 77030, TX, USA

    Vladislava O Melnikova, Svetlana V Bolshakov, Christopher Walker & Honnavara N Ananthaswamy

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Correspondence to Honnavara N Ananthaswamy.

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Melnikova, V., Bolshakov, S., Walker, C. et al. Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines. Oncogene 23, 2347–2356 (2004). https://doi.org/10.1038/sj.onc.1207405

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