Oct-3/4 is a dose-dependent oncogenic fate determinant.
The Oct-3/4 transcription factor sustains embryonic stem (ES) cell self-renewal and is a dose-dependent cell fate determinant. In the adult male, its expression is restricted to type A spermatogonia. We show that Oct-3/4 is expressed in all human testicular germ cell tumors (GCTs) tested, even in the early premalignant component. We demonstrate that Oct-3/4 dictates ES cells' oncogenic potential in a dose-dependent manner; high levels increase the malignant potential of ES cell-derived tumors while Oct-3/4 inactivation induces regression of the malignant component. Oct-3/4 expression in a heterologous cell system transforms nontumorigenic cells and endows tumorigenicity in nude mice. Our findings suggest that Oct-3/4 is not only a distinctive immunohistochemical marker for GCTs, but also plays a critical role in the genesis of these tumors.
Gidekel
Sharon
S
Department of Experimental Medicine and Cancer Research, The Hebrew University Hadassah Medical School, Jerusalem, Israel 91120.
Pizov
Galina
G
Bergman
Yehudit
Y
Pikarsky
Eli
E
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D018237:Germinoma / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D050814:Octamer Transcription Factor-3; D013093:Spermatogonia / Q000378:metabolism*; D013234:Stem Cells; D013737:Testis / Q000503:physiopathology; D014157:Transcription Factors / Q000378:metabolism*; D014183:Transplantation, Heterologous / Q000473:pathology
D004268:DNA-Binding Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors