NOTCH-ing up cancer genes

Notch receptor signaling has been implicated in cell-fate decisions and differentiation in a variety of tissues. In an Advanced Online Publication in Nature Genetics, Michael Nicolas and colleagues define a tumor suppressor function for the mouse Notch1 gene (Nature Genetics, DOI:10.1038/ng1099, 18 February, 2003).

As Notch1 is essential for embryonic development, Nicolas et al. used a tissue-specific inducible gene targeting approach to specifically delete the Notch1 gene in the skin. Notch1 ablation led to epidermal hyperproliferation and the development of basal cell carcinoma-like (BCC-like) tumors. This was unexpected as Notch signaling has been shown to cause tumors in other tissues. The Notch1-less mice were also susceptible to chemical-induced carcinogenesis. Tumors lacking Notch1 were associated with decrease levels of the CDK inhibitor p21Cip1 and elevated levels of Gli2 and components of the β-catenin/WNT pathway.