Oral squamous cell carcinoma (OSCC) develop multi-step carcinogenesis, including the concept of the field cancerization. DEK gene is considered to be a proto-oncogene, has multifaceted functions, such as replication, transcription, and chromatin remodeling, and also affects oncogenic process, such as cellular proliferation, differentiation, senescence, and apoptosis. DEK overexpression has proposed to be closely associated with many malignancies, however, functional mechanisms and crucial roles are still unclear. DEK-expressing cells significantly increased in human oral squamous cell carcinogenesis. We generated ubiquitous and squamous cell-specific Doxycycline (DOX)- inducible Dek mice (iDek and iDek-e mice, respectively). DOX administrated (DOX+) iDek mice promoted field cancerization and the development of OSCC in the environment exposed to carcinogen. By the microarray expression profiling analysis, the promotion of the filed cancerization by Dek overexpression was mediated by the upregulation of DNA replication- and cell cycle (G1 to S phase transition)-related genes. Further, Dek-overexpressed tongue tumors were progressed by proliferating cell nuclear antigen (Pcna) and the elongator complex protein 3 (Elp3). Our data suggest that, by DEK overexpression enhances the carcinogenesis, including field cancerization, of OSCC stimulating the G1-to-S phase transition in the cell-cycle and DNA replication, even after carcinogen-exposed environment, and offers a fascinating target for treatment and prevention of OSCC.
Overall design: For microarray analysis, total RNA (from mouse tongue tissue) was extracted with the Simply RNA tissue Kit (Promega, Fitchburg, Wisconsin (WI), USA) on a Maxwell RSC instrument. Gene expression analysis of the RNA samples was performed using by TAKARA Bio Inc. (Shiga, Japan) using Agilent Expression Array (SurePrint G3 Mouse GE 8 × 60 K Microarray). Two group2 (n=3 each) of Dek induced mice and Dek not induced mice
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