Oct-3/4 is a dose-dependent oncogenic fate determinant

Cancer Cell. 2003 Nov;4(5):361-70. doi: 10.1016/s1535-6108(03)00270-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Embryo, Mammalian
  • Germ Cells / cytology
  • Germ Cells / metabolism*
  • Germinoma / physiopathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Octamer Transcription Factor-3
  • Spermatogonia / metabolism*
  • Stem Cells
  • Testis / physiopathology
  • Transcription Factors / metabolism*
  • Transplantation, Heterologous / pathology


  • DNA-Binding Proteins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Pou5f1 protein, mouse
  • Transcription Factors