Cell cycle models for the aberrant coupling of growth arrest and differentiation in hyperplasia, metaplasia, and neoplasia.

The control of cell proliferation can be regulated by the coupling of growth arrest and differentiation. Since this process has been demonstrated both in vivo and in vitro, it is thought to be of considerable physiologic significance. The mechanisms that serve to couple growth arrest and differentiation were, however, poorly defined prior to our recent studies. We established that the coupling of growth arrest and differentiation of proadipocytes occurs at a distinct state in the G1 phase of the cell cycle, GD, and that it consists of at least five phases. These include: 1) growth arrest at GD; 2) nonterminal differentiation; 3) terminal differentiation; 4) loss of the differentiated phenotype, and 5) reinitiation of cell proliferation. On the basis of these observations we developed a cell cycle model to explain the biologic mechanisms of the coupling process. This model is now used to predict where defects in the coupling of growth arrest and differentiation may occur in hyperplastic, metaplastic, and neoplastic cells.