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

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 improving 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 overexpression in vivo, we generated and validated a tetracycline responsive Dek transgenic mouse model referred to as Bi-L-Dek. Dek overexpression was induced in the basal keratinocytes of stratified squamous epithelium by crossing Bi-L-Dek mice to keratin 5 tetracycline transactivator (K5-tTA) mice. Conditional transgene expression was validated in the resulting Bi-L-Dek_K5-tTA mice and was suppressed with doxycycline treatment in the tetracycline-off system. The mice were subjected to an established HNSCC and esophageal carcinogenesis protocol using the chemical carcinogen 4-nitroquinoline 1-oxide (4NQO). Dek overexpression stimulated gross esophageal tumor development, when compared to doxycycline treated control mice. Furthermore, high Dek expression caused a trend toward esophageal hyperplasia in 4NQO treated mice. Taken together, these data demonstrate that Dek overexpression in the cell of origin for SCC is sufficient to promote esophageal SCC development in vivo.

Dual- and Polytobacco/Nicotine Product Use Trends in a National Sample of High School Students.

PURPOSE: The study purpose was to examine changes in patterns of ever and current dual- and polyproduct use over time and to examine demographic and modifiable risk factors including tobacco smoke exposure (TSE). DESIGN: A secondary analysis of the 2013 to 2015 National Youth Tobacco Survey data. SETTING: Nationwide high schools were selected. SUBJECTS: A total of 31 022 high school students. MEASURES: Ever and current (past 30 days) tobacco/nicotine product use, home tobacco/nicotine product use, TSE and e-cigarette vapor exposure, and demographic characteristics were measured. ANALYSIS: Multivariable logistic regression and multinomial logistic regression models. RESULTS: Of the students, 9.4% were ever dual users and 18.6% were ever poly users. Rates of ever/current use of e-cigarettes and hookah increased from 2013 to 2015 (all Ps < .001). In 2015, participants were 4.8 times (95% confidence interval [CI], 4.5-5.2) and 4.0 times (95% CI, 3.5-4.4) more likely to report ever/current e-cigarette use and 1.61 times (95% CI, 1.5-1.7) and 1.48 times (95% CI, 1.3-1.7) more likely to report ever/current hookah use. Participants reporting TSE were 15.4 times (95% CI, 11.5-21.0) more likely to report current poly use, and those with e-cigarette exposure were 10.4 times (95% CI, 7.8-13.8) more likely to report current poly use. CONCLUSION: From 2013 to 2015, rates of ever and current use of e-cigarettes and hookah increased. Tobacco smoke and e-cigarette exposure were associated with higher rates of dual and poly use. Prevention efforts targeting these products are needed.