Cellular mechanisms for tumor promotion and enhancement.

The concepts of tumor promotion discussed in this chapter demonstrate the complexity of the tumor promotion process, and illustrate the difficulty of determining which events are mechanistically important to promotion, and which ones are the result, or by-product of promotion. A number of possible mechanisms of promotion, both epigenetic and genetic, have been described on a molecular level. However, it should be stressed that none of these mechanisms is mutually exclusive; indeed, the enormous complexity of tumor promotion suggests that several of the mechanisms discussed above may very well be interrelated. The effects on epidermal differentiation, for example, may turn out to be the result of altered expression of particular oncogene whose product is actually a growth factor able to select for and amplify certain subpopulations of cells. Furthermore, the multiple steps which may occur at the molecular level, perhaps by way of sequential gene activation, serve to mirror the multiple stages which now delineate carcinogenesis in mouse skin.