The anti-apoptotic gene survivin contributes to teratoma formation by human embryonic stem cells.
Teratomas derived from human embryonic stem (hES) cells are unique among oncogenic phenomena as they are polyclonal and develop from apparently normal cells. A deeper understanding of this process should aid in the development of safer cell therapies and may help elucidate the basic principles of tumor initiation. We find that transplantation of diploid hES cells from four independent cell lines generates benign teratomas with no sign of malignancy or persisting embryonal carcinoma-like cells. In contrast, mouse embryonic stem (mES) cells from four cell lines consistently generate malignant teratocarcinomas. Global gene expression analysis shows that survivin (BIRC5), an anti-apoptotic oncofetal gene, is highly expressed in hES cells and teratomas but not in embryoid bodies. Genetic and pharmacological ablation of survivin induces apoptosis in hES cells and in teratomas both in vitro and in vivo. We suggest that continued expression of survivin upon differentiation in vivo may contribute to teratoma formation by hES cells.
Blum
Barak
B
Stem Cell Unit, Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
Bar-Nur
Ori
O
Golan-Lev
Tamar
T
Benvenisty
Nissim
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D013724:Teratoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D000077022:Survivin