Experimental models and biological mechanisms for tumor promotion.

Studies of skin tumor induction in the mouse have demonstrated that the process of carcinogenesis can be divided into two discrete stages: initiation and promotion. Research over the last twenty years has shown that this two-stage model generally applies to tumor induction in epithelial tissues. In many cases, the initiating event is the induction of a dominant mutation in a cellular proto-oncogene. The promotion stage is complex, and represents a composite of events involving alteration in the expression of specific genes, proliferation of the initiated cell and its clonal descendants, and accumulation of additional genetic alterations.