Skin deep

Fundamental differences between human and murine skin, and differences in cellular transformation, pose a challenge to the development of useful models to study skin diseases and malignancies. In the February 6 Nature, Maya Dajee and colleagues at Stanford University School of Medicine, California, USA, describe experiments in normal epidermal cells that demonstrate the roles of oncogenic Ras and NFκB pathways in neoplastic transformation (Nature, 421:639-643, February 6, 2003).

Dajee et al. used an animal model in which normal human skin is grafted onto the back of immunodeficient scid mice. They delivered a series of oncogenic genes to human keratinocytes using retroviral infections. Co-expression of oncogenic Ras and a stable repressor mutant of IκBα induced large neoplasms similar to human squamous cell carcinoma (SCC). The tumors displayed several SCC characteristics including an elevated mitotic index.

Blocking NFκB activity appeared to overcome Ras-induced growth arrest and induced high levels of CDK4. They ...