Tumor suppressor genes.

Although tumor suppressor genes continue to be discovered, the most recent advances have been made in attributing new and exciting functions to existing ones - such as the apparent role of VHL as a regulator of proteolysis. Great insights have also come from piecing genes together into pathways and networks. For instance the discovery that cyclin D1 is regulated by beta-catenin/Tcf-4 allows us to tie the APC pathway to the RB pathway and cell cycle control. Similarly, tumor suppressor genes have been fitted together with oncogenes into the various pathways that regulate apoptosis such that tumor suppressor function is now attributed to some of the basic components of the apoptotic machinery, such as caspases and Apaf-1. The great pace at which mouse models of tumorigenesis continue to advance our knowledge of tumor suppressor gene function has led us to look anew at the role of genes such as TCF-1 and SMAD-3 in human cancer. Finally, the realisation that different growth regulatory pathways give rise to generic signals suggests that future work may lie in integrating the signals from different pathways and in understanding the importance of protein levels to cellular function.