The biological role of the Fas/FasL system during tumor

Loss of Fas and gain of aberrant FasL expression are common features of malignant transformation. Lost of Fas expression is thereby a prerequisite of aberrant FasL expression, which would otherwise induce suicide or fratricide among tumor cells. The notion of loss of Fas function as an oncogenic event is further supported by the observation that other factors implicated in malignant progression, i.e. mutation of ras or p53 genes, downregulate Fas expression. Furthermore, germline mutations of the Fas gene in the human are associated not only with lymphoproliferation and autoimmunity but also witha highrisk of lymphoid and solid tumors.

Based on these insights, one can conclude that an understanding of the mechanisms controlling and implementing apoptosis is more than a matter of mere scientific interest. Apoptosis is an essential component of most human diseases and, in many cases, the underlying cause of the resulting pathology. Disorders associated withinsufficient cell deathinclude autoimmunity and cancer. In such cases, reinstating the blocked or defective apoptotic program is likely to have an enormous impact on the disease. Thus, the conservation of the apoptotic machinery through evolution has provided us witha wealthof experimental systems to study, understand, and eventually manipulate this fundamental biological process.