A mouse model of human oral-esophageal cancer

J Clin Invest. 2002 Sep;110(6):761-9. doi: 10.1172/JCI15324.


Squamous cancers of the oral cavity and esophagus are common worldwide, but no good genetically based animal model exists. A number of environmental factors as well as genetic alterations have been identified in these cancers, yet the specific combination of genetic events required for cancer progression remains unknown. The Epstein-Barr virus ED-L2 promoter (L2) can be used to target genes in a specific fashion to the oral-esophageal squamous epithelium. To that end, we generated L2-cyclin D1 (L2D1(+)) mice and crossbred these with p53-deficient mice. Whereas L2D1(+) mice exhibit a histologic phenotype of oral-esophageal dysplasia, the combination of cyclin D1 expression and p53 deficiency results in invasive oral-esophageal cancer. The development of the precancerous lesions was significantly reversed by the application of sulindac in the drinking water of the L2D1(+)/p53(+/-) mice. Furthermore, cell lines derived from oral epithelia of L2D1(+)/p53(+/-) and L2D1(+)/p53(-/-) mice, but not control mice, formed tumors in athymic nude mice. These data demonstrate that L2D1(+)/p53(+/-) mice provide a well-defined, novel, and faithful model of oral-esophageal cancer, which allows for the testing of novel chemopreventive, diagnostic, and therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Disease Models, Animal*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Genotype
  • Herpesvirus 4, Human / genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Neoplasms, Squamous Cell / drug therapy
  • Neoplasms, Squamous Cell / genetics*
  • Neoplasms, Squamous Cell / pathology
  • Promoter Regions, Genetic
  • Sulindac / therapeutic use
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • Antineoplastic Agents
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Sulindac
  • ErbB Receptors