Melanoma Proliferation and Chemoresistance Controlled by the DEK Oncogene (original) (raw)

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 (i.e. within common melanomaamplified 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 upregulation of DEK protein in cells from aggressive melanomas. 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 downregulation by independent shRNAs 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 shRNA had no impact 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-x L were unaffected by changes in the endogenous levels of DEK, indicating a selective impact of this gene on the apoptotic machinery of melanoma * Requests for reprints: María S. Soengas, Centro Nacional de Investigaciones Oncológicas, CNIO, Melchor Fernández Almagro 3. Madrid 28049, Spain. Phone: 34-91-732 8000-Ext 3680. msoengas@cnio.es