Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo
| Autor: | Trisha Wise-Draper, Teresa A. Morris, Susanne I. Wells, Timothy P. Cripe, Mark A. Currier, David S. Simpson, Gerard Grosveld, Rachael A. Mintz-Cole, Kathryn A. Wikenheiser-Brokamp |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Chromosomal Proteins Non-Histone Papillomavirus E7 Proteins Apoptosis Biology medicine.disease_cause Article Small hairpin RNA Mice Transcription (biology) Cell Line Tumor Neoplasms medicine Animals Humans Poly-ADP-Ribose Binding Proteins Oncogene Proteins Oncogene Papilloma Cell growth Oncogene Proteins Viral Molecular biology Cell biology DNA-Binding Proteins Mice Inbred C57BL Repressor Proteins stomatognathic diseases Cell Transformation Neoplastic Oncology Knockout mouse Tumor promotion Female Carcinogenesis |
| Zdroj: | Cancer research. 69(5) |
| ISSN: | 1538-7445 |
| Popis: | High levels of expression of the human DEK gene have been correlated with numerous human malignancies. Intracellular DEK functions have been described in vitro and include DNA supercoiling, DNA replication, RNA splicing, and transcription. We have shown that DEK also suppresses cellular senescence, apoptosis, and differentiation, thus promoting cell growth and survival in monolayer and organotypic epithelial raft models. Such functions are likely to contribute to cancer, but direct evidence to implicate DEK as an oncogene has remained elusive. Here, we show that in line with an early role in tumorigenesis, murine papilloma formation in a classical chemical carcinogenesis model was reduced in DEK knockout mice. Additionally, human papillomavirus E6/E7, hRas, and DEK cooperated in the transformation of keratinocytes in soft agar and xenograft establishment, thus also implicating DEK in tumor promotion at later stages. Finally, adenoviral DEK depletion via short hairpin RNA expression resulted in cell death in human tumor cells in vitro and in vivo, but did not significantly affect differentiated epithelial cells. Taken together, our data uncover oncogenic DEK activities as postulated from its frequent up-regulation in human malignancies, and suggest that the targeted suppression of DEK may become a strategic approach to the treatment of cancer. [Cancer Res 2009;69(5):1792–9] |
| Databáze: | OpenAIRE |
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