Promotion of cell proliferation by the proto-oncogene DEK enhances oral squamous cell carcinogenesis through field cancerization.

ABSTRACT: Oral squamous cell carcinoma (OSCC) develops through a multistep carcinogenic process involving field cancerization. The DEK gene is a proto-oncogene with functions in genetic and epigenetic modifications, and has oncogenic functions, including cellular proliferation, differentiation, and senescence. DEK overexpression is associated with malignancies; however, the functional roles of DEK overexpression are unclear. We demonstrated that DEK-expressing cells were significantly increased in human dysplasia/carcinoma in situ and OSCC. Furthermore, we generated ubiquitous and squamous cell-specific doxycycline (DOX)-inducible Dek mice (iDek and iDek-e mice respectively). Both DOX+ iDek and iDek-e mice did not show differences in the oral mucosa compared with DOX- mice. In the environment exposed to carcinogen, DOX-treated (DOX+) iDek mice showed field cancerization and OSCC development. Microarray analysis revealed that DEK overexpression was mediated by the upregulation of DNA replication- and cell cycle-related genes, particularly those related to the G₁ /S transition. Tongue tumors overexpressing DEK showed increased proliferating cell nuclear antigen and elongator complex protein 3 expression. Our data suggest that DEK overexpression enhanced carcinogenesis, including field cancerization, in OSCC by stimulating the G₁ /S phase transition and promoting DNA replication, providing important insights into the potential applications of DEK as a target in the treatment and prevention of OSCC.

SUBMITTER: Nakashima T 

PROVIDER: S-EPMC5633549 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature