Antisense Strategies for Modulating the Repression of Cell Division

Investigations on the regulation of cell division require both genetic studies to identify crucial steps in the process and biochemical studies to assign a particular function to the identified protein. As genetic studies are difficult to carry out in the mammalian system most of the hitherto known regulatory proteins were first identified in yeast and their presence and function was subsequendy confirmed in mammalian cells. However, human cancers provide a source for naturally occuring mutations in genes which are related to the regulation of cell division. The products of protooncogenes which are changed in their function or activity in particular cancers are mainly known as positive regulators or modulators of cell division (Hunter 1991). Tumor suppressor genes were identified by their loss in certain cancers and are supposed to be negative regulators of cell division in normal cells (Weinberg 1991). The current view of cancer development, however, implies two or more subsequent genetic changes (Fearon and Vogelstein 1990, Marshall 1991) making the cancer cell itself an unsuitable system for studying the direct consequences of the respective changes. Thus, alternative ways for the inactivation of gene functions are required.