Melanoma Proliferation and Chemoresistance Controlled by the DEK Oncogene
| العنوان: | Melanoma Proliferation and Chemoresistance Controlled by the DEK Oncogene |
|---|---|
| المؤلفون: | Michael S. Khodadoust, Ferdinand Kappes, David S.L. Kim, David M. Markovitz, Arul M. Chinnaiyan, Maria S. Soengas, Monique Verhaegen, Juan C. Cigudosa, Erica Riveiro-Falkenbach |
| المصدر: | Cancer Research. 69:6405-6413 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Cancer Research, Skin Neoplasms, Oncogene Proteins, Chromosomal Proteins, Non-Histone, bcl-X Protein, Chromatin Remodeling Factor, Biology, Article, Small hairpin RNA, medicine, Humans, RNA, Small Interfering, Poly-ADP-Ribose Binding Proteins, Melanoma, Cells, Cultured, Cellular Senescence, Cell Proliferation, Oncogene, Cell growth, medicine.disease, Phenotype, Gene Expression Regulation, Neoplastic, stomatognathic diseases, Proto-Oncogene Proteins c-bcl-2, Oncology, Drug Resistance, Neoplasm, Cancer research, Myeloid Cell Leukemia Sequence 1 Protein, Chromosomes, Human, Pair 6, Tumor Suppressor Protein p53, Cell aging |
| الوصف: | Gain of chromosome 6p is a consistent feature of advanced melanomas. However, the identity of putative oncogene(s) associated with this amplification has remained elusive. The chromatin remodeling factor DEK is an attractive candidate as it maps to 6p (within common melanoma-amplified loci). Moreover, DEK expression is increased in metastatic melanomas, although the functional relevance of this induction remains unclear. Importantly, in other tumor types, DEK can display various tumorigenic effects in part through its ability to promote proliferation and inhibit p53-dependent apoptosis. Here, we report a generalized up-regulation of DEK protein in aggressive melanoma cells and tumors. In addition, we provide genetic and mechanistic evidence to support a key role of DEK in the maintenance of malignant phenotypes of melanoma cells. Specifically, we show that long-term DEK down-regulation by independent short hairpin RNAs resulted in premature senescence of a variety of melanoma cell lines. Short-term abrogation of DEK expression was also functionally relevant, as it attenuated the traditional resistance of melanomas to DNA-damaging agents. Unexpectedly, DEK short hairpin RNA had no effect on p53 levels or p53-dependent apoptosis. Instead, we identified a new role for DEK in the transcriptional activation of the antiapoptotic MCL-1. Other MCL-1–related factors such as BCL-2 or BCL-xL were unaffected by changes in the endogenous levels of DEK, indicating a selective effect of this gene on the apoptotic machinery of melanoma cells. These results provide support for DEK as a long sought-after oncogene mapping at chromosome 6, with novel functions in melanoma proliferation and chemoresistance. [Cancer Res 2009;69(16):6405–13] |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-09-1063 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1922b25f2c85df13fb37f5c8ac40e3c1 https://doi.org/10.1158/0008-5472.can-09-1063 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1922b25f2c85df13fb37f5c8ac40e3c1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/0008-5472.can-09-1063 |