Transgenic mouse model for skin malignant melanoma

Oncogene. 1998 Oct 8;17(14):1885-8. doi: 10.1038/sj.onc.1202077.


We report here on a novel metallothionein-I (MT)/ret transgenic mouse line in which skin melanosis, benign melanocytic tumor and malignant melanoma metastasizing to distant organs develop stepwise. The process of tumor development and its malignant transformation in this line may resemble that of the human giant congenital melanocytic nevus that is present at birth and that frequently gives rise to malignant melanoma during aging. We observed an increase in the expression level and activity of the ret transgene during the disease progression. That increase in transgene expression accompanied an activation of mitogen-activated protein kinases (MAPKs) and c-Jun as well as matrix metalloproteinases. These results suggest that progressive dysregulation of the expression level of the ret transgene might play a crucial role in the malignant transformation of melanocytic tumors developed in the MT/ret transgenic mouse line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Melanoma, Experimental* / metabolism
  • Melanoma, Experimental* / pathology
  • Metallothionein / genetics
  • Metallothionein / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-jun
  • Metallothionein
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1