Induction of squamous cell carcinoma after MAP3K8 overexpression in murine salivry gland epithelial cells

Head Neck. 2019 Apr;41(4):924-929. doi: 10.1002/hed.25411. Epub 2019 Feb 5.

Abstract

Background: Salivary gland neoplasms are relatively rare and comprise only 1%-4% of all human neoplasms. Salivary gland neoplasms also show an extremely wide range of morphological diversity. Currently, the genetic alterations and corresponding molecular mechanisms underlying salivary gland neoplasms development remain largely unknown.

Method: We generated an inducible Tet-MAP3K8::MMTV-rTA mouse model by crossing the MAP3K8 transgenic mice with MMTR-rTA transgenic mice to express MAP3K8 in the salivary gland.

Results: MAP3K8 overexpression in the murine salivary glands of Tet-MAP3K8::MMTR-rTA transgenic mice induces tumorigenesis. Pathological investigations reveal partial fibrosis and adenosis of salivary glands, and foci of atypical squamoid cellular proliferation, which represent invasive squamous cell carcinoma (SCC).

Conclusion: MAP3K8 overexpression is associated with SCC development in murine salivary glands. It provides an in vivo framework for the understanding of molecular mechanisms underlying SCC development in the salivary glands and also for the development of a future therapeutic strategy targeting this tumor type.

Keywords: MAP3K8; salivary gland; squamous cell carcinoma; transgenic mouse; tumorigenesis.

MeSH terms

  • Animals
  • Biopsy, Needle
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Cells, Cultured
  • Disease Models, Animal
  • Epithelial Cells
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • MAP Kinase Kinase Kinases / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / genetics*
  • Random Allocation
  • Republic of Korea
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / pathology*
  • Sensitivity and Specificity
  • Up-Regulation / genetics*

Substances

  • Proto-Oncogene Proteins
  • MAP Kinase Kinase Kinases
  • Map3k8 protein, mouse