Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation

Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1480-5. doi: 10.1073/pnas.0510652103. Epub 2006 Jan 23.


PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in a murine model of prostate cancer recapitulates the disease progression seen in humans. Using defined cell lineage markers, we demonstrate that PTEN negatively regulates p63-positive prostatic basal cell proliferation without blocking differentiation. Concomitant with basal cell proliferation is the expansion of a prostate stem/progenitor-like subpopulation as evidenced by the progressive increase of stem cell antigen-1 (Sca-1)- and BCL-2-positive cells. This observation provides strong evidence that basal cell proliferation can be an initiating event for precancerous lesions. Sca-1(+) and BCL-2(+) progenitors may serve as cancer-initiating cells in this model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bromodeoxyuridine / pharmacology
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cell Separation
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Disease Progression
  • Flow Cytometry
  • Gene Deletion
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis
  • Kinetics
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Neoplasms / metabolism
  • PTEN Phosphohydrolase / metabolism
  • PTEN Phosphohydrolase / physiology*
  • Phosphoproteins / metabolism
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Stem Cells / cytology*
  • Time Factors
  • Trans-Activators / metabolism
  • Transcription Factors
  • Tumor Suppressor Proteins


  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Phosphoproteins
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Trp63 protein, mouse
  • Tumor Suppressor Proteins
  • PTEN Phosphohydrolase
  • Bromodeoxyuridine