Nature Medicine
3, 917 - 921 (1997)
doi:10.1038/nm0897-917
A novel anti-apoptosis gene, survivin, expressed in cancer and lymphomaGrazia Ambrosini1, Colette Adida1
& Dario C. Altieri1, 2
1Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06536
2Correspondence should be addressed to D.C.A. Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer1 by facilitating the insurgence of mutations and by promoting resistance to therapy2. Despite the identification of several new apoptosis inhibitors related to bcl-22,3 or to the baculovirus IAP gene4−9, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.
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