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

Promotion of cell proliferation by the proto-oncogene DEK enhances oral squamous cell carcinogenesis through field cancerization.
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Nakashima T, Tomita H, Hirata A, Ishida K, Hisamatsu K, Hatano Y, Kanayama T, Niwa A, Noguchi K, Kato K, Miyazaki T, Tanaka T, Shibata T, Hara A,


Nakashima T, Tomita H, Hirata A, Ishida K, Hisamatsu K, Hatano Y, Kanayama T, Niwa A, Noguchi K, Kato K, Miyazaki T, Tanaka T, Shibata T, Hara A, (click to view)

Nakashima T, Tomita H, Hirata A, Ishida K, Hisamatsu K, Hatano Y, Kanayama T, Niwa A, Noguchi K, Kato K, Miyazaki T, Tanaka T, Shibata T, Hara A,

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Cancer medicine 2017 08 23() doi 10.1002/cam4.1157
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.

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