Neural- and Endocrine-Cell-Specific Immortalization Using Transgenic Approaches

During development, in response to a wide range of intracellular and extracellular signals, eukaryotic cells choose a spectrum of “fates.” Under normal physiological conditions, cells grow, progress through a series of cell cycle events, divide, and differentiate (1,2). Depending upon the cell type and the terminally differentiated function, a fraction of cells also undergo apoptosis (i.e., cell death) or cell-cycle arrest, until they are activated by specific stimuli and re-enter the cell cycle (1,2). Overall, the cell phenotypes are dictated and governed by a balanced activity between various positive regulators (growth factors, oncogenes) and negative regulators (tumor suppressors) of the cell cycle (1,2). Aberrant activities of either of these regulators result in excessive proliferation, leading to immortalization at the cellular level and the initiation of tumors at the organism level. Alternatively, cells may undergo accelerated senescence and eventually die because of these aberrant events (1, 2). Molecular analysis of these critical events has many implications in understanding the origin and nature of human cancers and possible therapeutic intervention and cure by various genetic approaches.