Defining the molecular mechanisms of human cell immortalization.

Although the immortalization of human cells is a key step in oncogenic progression, the molecular mechanisms underlying this event are poorly understood. After reviewing the use of chemicals, physical agents, oncogenes and DNA tumor viruses as immortalizing agents, we consider the importance of negative regulators of cell growth (RB and p53), their inactivation, as well as genomic instability in the pathogenesis of cancer. Finally, a molecular model for human cell immortalization that integrates many of the above observations is presented along with supporting evidence.