Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression

Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11563-8. doi: 10.1073/pnas.201167798. Epub 2001 Sep 11.


The PTEN gene encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase pathway and is inactivated in a wide variety of malignant neoplasms. High rates of loss of heterozygosity are observed at the 10q23.3 region containing the human PTEN gene in prostate cancer and other human malignancies, but the demonstrated rate of biallelic inactivation of the PTEN gene by mutation or homozygous deletion is significantly lower than the rate of loss of heterozygosity. The transgenic adenocarcinoma of mouse prostate model is a well characterized animal model of prostate cancer. Analysis of prostate cancer progression in transgenic adenocarcinoma of mouse prostate mice bred to Pten(+/-) heterozygous mice, coupled with analysis of the Pten gene and protein in the resulting tumors, reveals that haploinsufficiency of the Pten gene promotes the progression of prostate cancer in this model system. This observation provides a potential explanation for the discordance in rates of loss of heterozygosity at 10q23 and biallelic PTEN inactivation observed in prostate cancer and many human malignancies.

Publication types

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

MeSH terms

  • Animals
  • Disease Progression
  • Genes, Tumor Suppressor*
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / deficiency
  • Phosphoric Monoester Hydrolases / genetics*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Survival Rate
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / genetics*


  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human