Anti-apoptotic Bcl-2 proteins: structure, function and relevance for radiation biology

Purpose: Bcl-2 family members mediate anti-apoptotic signals in a wide variety of human cell systems. Despite its proven antiapoptotic function, several results indicate that overexpression of Bcl-2 is not clearly associated with increased radiation resistance in vitro or in vivo. The reasons for this obvious contradiction are not understood. Materials and methods: Current data on the function of Bcl-2 as an anti-apoptotic protein, its role for the modulation of radiation sensitivity in vitro and its value as prognostic marker in vivo are reviewed. Results: Bcl-2 and related proteins are currently perceived to be the most important anti-apoptotic proteins. Their function is related to their ability to interfere with mitochondrial apoptosis pathways. Contradictory data have been published on the relevance of Bcl-2 and related family members for in vitro and in vivo tumour response. The value of Bcl-2 as a prognostic marker thus remains unclear. Conclusions : Although Bcl-2-related proteins are currently the most relevant anti-apoptotic modulators, their relevance for radiation responses in vivo or in vitro remain undefined. Furthermore, their determination in a routine clinical setting does not appear to be justified.