Pathways sufficient to induce epidermal carcinogenesis

Abnormal epidermal proliferation is characteristic of a number of disorders, including the two most common cancers in the United States, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Both cancers display a disruption in the normal homeostatic balance between cell division and programmed cell death. While abnormal activation of the sonic hedgehog/patched pathway has been established as sufficient to induce hallmark features of BCC in both human and murine epidermis, pathways sufficient to convert normal epidermis into SCC have been less well defined. Building on findings that indicate a potent role for Ras and NF-kappaB in normal epidermal growth regulation, recent work indicates that activation of Ras signaling in concert with inhibition of NF-kappaB function is entirely sufficient to transform normal human epidermis into tumor tissue with all the cardinal features of SCC.