Regulatory imbalances in cell proliferation and cell death during oncogenesis in transgenic mice

Whether a cell decides to proliferate, undergo growth arrest, or even commit suicide is determined by a multitude of highly potent positive and negative regulatory factors. Mutational perturbation of these factors and the normal pathways through which they regulate either cell proliferation or cell death can induce a pathologic enhancement in cell number, or hyperplasia, and eventually the development of malignant tumors. Serving as valuable animal models for cancer in humans, transgenic mice have been used to demonstrate the dramatic consequences of subverting the normal molecular mechanisms regulating cell proliferation and/or cell death. This review will use three transgenic mouse models to illustrate the consequences of inducing such regulatory imbalances, as well as the utility and versatility of the transgenic approach in cancer research. Three different regulatory factors are considered; transforming growth factor-alpha is discussed as an example of a positive growth regulator, p53 as a negative growth regulator, and Bcl-2 as an inhibitor of programmed cell death.