Dek overexpression in murine epithelia increases overt esophageal squamous cell carcinoma incidence

by Marie C. Matrka, Katherine A. Cimperman, Sarah R. Haas, Geraldine Guasch, Lisa A. Ehrman, Ronald R. Waclaw, Kakajan Komurov, Adam Lane, Kathryn A. Wikenheiser-Brokamp, Susanne I. Wells Esophageal cancer occurs as either squamous cell carcinoma (ESCC) or adenocarcinoma. ESCCs comprise almost 90% of cases worldwide, and recur with a less than 15% five-year survival rate despite available treatments. The identification of new ESCC drivers and therapeutic targets is critical for imp roving outcomes. Here we report that expression of the human DEK oncogene is strongly upregulated in esophageal SCC based on data in the cancer genome atlas (TCGA). DEK is a chromatin-associated protein with important roles in several nuclear processes including gene transcription, epigenetics, and DNA repair. Our previous data have utilized a murine knockout model to demonstrate that Dek expression is required for oral and esophageal SCC growth. Also, DEK overexpression in human keratinocytes, the cell of origin for SCC, was sufficient to cause hyperplasia in 3D organotypic raft cultures that mimic human skin, thus linking high DEK expression in keratinocytes to oncogenic phenotypes. However, the role of DEK over-expression in ESCC development remains unknown in human cells or genetic mouse models. To define the consequences of Dek overexpressionin vivo, we generated and validated a tetracycline responsiveDek transgenic mouse model referred to asBi-L-Dek. Dek overexpression was induced in the bas...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research