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

Cancer Med. 2017 Oct;6(10):2424-2439. doi: 10.1002/cam4.1157. Epub 2017 Aug 23.


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.

Keywords: DEK; field cancerization; oncogene; squamous cell carcinoma.

MeSH terms

  • Animals
  • Carcinogens / administration & dosage*
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Chromosomal Proteins, Non-Histone / genetics*
  • Disease Models, Animal
  • Embryonic Stem Cells / metabolism
  • Gene Expression
  • Humans
  • Mice
  • Models, Biological
  • Mouth Neoplasms / etiology*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Oncogene Proteins / genetics*
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Mas


  • Carcinogens
  • Chromosomal Proteins, Non-Histone
  • Dek protein, human
  • MAS1 protein, human
  • Oncogene Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Mas