Overexpression of survivin initiates hematologic malignancies in vivo.
Survivin is an inhibitor of apoptosis protein family member that has an essential role in cellular proliferation as a component of the chromosome passenger complex. Survivin is highly expressed in embryos and in proliferating adult tissues, but it is not expressed in most differentiated cells. During tumorigenesis, however, survivin expression is dramatically upregulated. Although many studies have shown that survivin is required for cancer cells, the extent to which survivin contributes to the initiation of tumors is unknown. Here we show that transgenic mice that overexpress survivin in hematopoietic cells are at an increased risk of hematologic tumors. In examining how survivin might contribute to tumorigenesis, we observed that hematopoietic cells engineered to overexpress survivin are less susceptible to apoptosis. We conclude that survivin may promote tumorigenesis by imparting a survival advantage to cells that acquire additional genetic lesions.
Small
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Division of Hematology and Oncology, Northwestern University Chicago, Chicago, IL 60611, USA.
Keerthivasan
G
G
Huang
Z
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Gurbuxani
S
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Crispino
J D
JD
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D002470:Cell Survival; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000276:immunology; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
C107489:BIRC5 protein, human; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin