Specific c-Jun target genes in malignant melanoma
Schummer P, Kuphal S, Vardimon L, Boßerhoff AK, Kappelmann M (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Publisher: Landes Bioscience
Book Volume: 17
Pages Range: 486-97
Journal Issue: 5
DOI: 10.1080/15384047.2016.1156264
Abstract
A fundamental event in the development and progression of malignant melanoma is the de-regulation of cancer-relevant transcription factors. We recently showed that c-Jun is a main regulator of melanoma progression and, thus, is the most important member of the AP-1 transcription factor family in this disease. Surprisingly, no cancer-related specific c-Jun target genes in melanoma were described in the literature, so far. Therefore, we focused on pre-existing ChIP-Seq data (Encyclopedia of DNA Elements) of 3 different non-melanoma cell lines to screen direct c-Jun target genes. Here, a specific c-Jun antibody to immunoprecipitate the associated promoter DNA was used. Consequently, we identified 44 direct c-Jun targets and a detailed analysis of 6 selected genes confirmed their deregulation in malignant melanoma. The identified genes were differentially regulated comparing 4 melanoma cell lines and normal human melanocytes and we confirmed their c-Jun dependency. Direct interaction between c-Jun and the promoter/enhancer regions of the identified genes was confirmed by us via ChIP experiments. Interestingly, we revealed that the direct regulation of target gene expression via c-Jun can be independent of the existence of the classical AP-1 (5´-TGA(C/G)TCA-3´) consensus sequence allowing for the subsequent down- or up-regulation of the expression of these cancer-relevant genes. In summary, the results of this study indicate that c-Jun plays a crucial role in the development and progression of malignant melanoma via direct regulation of cancer-relevant target genes and that inhibition of direct c-Jun targets through inhibition of c-Jun is a potential novel therapeutic option for treatment of malignant melanoma.
Authors with CRIS profile
Silke Kuphal
Lehrstuhl für Biochemie und Molekulare Medizin
Anja Katrin Boßerhoff
Lehrstuhl für Biochemie und Molekulare Medizin
Melanie Kappelmann-Fenzl
Emil-Fischer-Zentrum (Emil Fischer Center)
Involved external institutions
Israel (IL)How to cite
APA:
Schummer, P., Kuphal, S., Vardimon, L., Boßerhoff, A.K., & Kappelmann, M. (2016). Specific c-Jun target genes in malignant melanoma. Cancer Biology & Therapy, 17(5), 486-97. https://doi.org/10.1080/15384047.2016.1156264
MLA:
Schummer, Patrick, et al. "Specific c-Jun target genes in malignant melanoma." Cancer Biology & Therapy 17.5 (2016): 486-97.
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