Proliferation, senescence, and neoplastic progression of beta cells in hyperplasic pancreatic islets.

Three different cases of pancreatic beta cell hyperplasia in mice are accompanied by an increase in a subclass of cells expressing tyrosine hydroxylase (TH), a neuronal enzyme. In the nontumorigenic cases of islet growth during normal pregnancy and in the obese mutant mouse, the TH-insulin cells do not divide, in contrast to the "insulin-only" cells. In later stages the number of proliferating insulin-only cells decreases concomitant with an increase in the number of nondividing TH-insulin cells, suggesting that the TH-insulin cells are on a pathway to senescence. In the presence of an oncoprotein the TH-insulin cells are able to proliferate. The proliferation of this cell type may represent an escape from the senescence pathway and progression to immortal tumor cells.