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Increased gene Ccpy number may alter E2F1 activity in melanoma growth.
Nelson MA; Beas A; Goulet A; Lowry DT; Reynolds SH; Jefferson AM; Senft JR; Sargent L
Proceedings of the American Association for Cancer Research. 1st ed. Philadelphia, PA: American Association for Cancer Research, 2003 Mar; 44:273
The identification of recurring translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. Previous studies by our group identified translocations der(12)t(12;20) in malignant melanoma cells. The transcription factor E2F1 maps to 20q11. Deregulated E2F transcriptional activity has been associated with the autonomous growth of melanoma cells, but the molecular basis has not yet been elucidated. To this end, we investigated E2F1 gene copy number and structure in nine different early passage human melanoma cell lines. Fluorescent in situ hybridization analysis using a specific E2F1 probe indicated increased E2F1 gene copies in several melanoma cell lines compared to normal melanocytes. The FISH observations were confirmed by comparative genomic hybridization array to BAC clones and Southern Blot analysis. In addition, Western blot analysis demonstrated increased E2F1 and DP-1 protein levels in 8 out of 9 melanoma cells compared to normal melanocytes. These data suggests that the release of E2F activity by elevated E2F1 gene copy numbers may play a functional role in melanoma growth.
Neoplastic agents; Neoplastic transformation; Genes; Cancer; In situ combustion; Skin cancer
Abstract; Conference/Symposia Proceedings
94th Annual Meeting, Proceedings of the American Association for Cancer Research
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