Recently, a novel antiapoptosis gene, i.e., survivin, was identified as a 
structurally unique member of the inhibitor of apoptosis protein family. 
Survivin expression is turned off during fetal development and not found in 
non-neoplastic adult human tissues but is again turned on in the most common 
human cancers. The antiapoptotic properties of survivin might provide a 
significant growth advantage in tumors and possibly also contribute to 
chemoresistance of cancer. Therefore, we analyzed the expression of survivin in 
human renal cell carcinomas (RCCs), known to be largely resistant to 
chemotherapy. Northern blot analysis and RT-PCR revealed survivin expression in 
newly established RCC cell lines (n = 11) of all major histological types. 
Moreover, we identified two novel splice variants of survivin, lacking exon 3 
(survivin-deltaEx3) or retaining a part of intron 2 as a cryptic exon 
(survivin-2B). Both sequence alterations cause marked changes in the structure 
of the corresponding proteins, including structural modifications of the 
baculovirus inhibitor of apoptosis protein repeat domain. The role of the novel 
isoforms in the regulation of apoptosis was assessed in transfection 
experiments, showing conservation of antiapoptotic properties for 
survivin-deltaEx3 and a markedly reduced antiapoptotic potential for 
survivin-2B. In conclusion, our observations suggest a complex regulatory 
balance between the different isoforms of survivin, which might determine the 
response to proapoptotic stimuli, not only in human RCCs but also in fetal 
tissues and other types of cancer.