Increased gene copy number of The transcription factor E2F1 In malignant melanoma
| Autor: | Anthony Beas, Uma N.M. Rao, Yongmei Feng, Mark A. Nelson, Jamie R. Senft, Linda M. Sargent, Steven H. Reynolds, Barbara Honchak, Amy M. Jefferson, Robert C. Johnson, Anne Christine Goulet, Jim Averill, David T. Lowry |
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| Rok vydání: | 2006 |
| Předmět: |
endocrine system
Cancer Research Blotting Western Biology Translocation Genetic RNA interference Cell Line Tumor Gene duplication medicine Humans E2F1 Genetic Predisposition to Disease Copy-number variation Melanoma neoplasms Gene In Situ Hybridization Fluorescence Pharmacology Chromosomes Human Pair 12 Cell growth medicine.disease Molecular biology Oncology Cell culture Lymphatic Metastasis Cancer research Melanocytes Molecular Medicine RNA Interference biological phenomena cell phenomena and immunity E2F1 Transcription Factor |
| Zdroj: | Cancer Biology & Therapy. 5:407-412 |
| ISSN: | 1555-8576 1538-4047 |
| DOI: | 10.4161/cbt.5.4.2512 |
| Popis: | Translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. We have previously shown a unique translocation in malignant melanoma cells der(12)t(12;20). The transcription factor E2F1 maps to 20q11. Increased expression of E2F has been associated with the autonomous growth of melanoma cells, however, the molecular basis has not yet been elucidated. To this end, we investigated E2F1 gene copy number and structure in human melanoma cell lines and metastatic melanoma cases. Fluorescent in situ hybridization (FISH) analysis using a specific E2F1 probe indicated increased E2F1 gene copies in melanoma cell lines compared to normal melanocytes. We also observed increased copies of the E2F1 gene in lymph node metastases of melanoma. In addition, Western blot analysis demonstrated increased E2F1 protein levels in 8 out of 9 melanoma cell lines relative to normal melanocytes. Inhibition of E2F1 expression with RNAi also reduced melanoma cell growth. Our results suggest that the release of E2F activity by elevated E2F1 gene copy numbers may play a functional role in melanoma growth. |
| Databáze: | OpenAIRE |
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