Expression of mTOR signaling pathway markers in prostate cancer progression

Prostate. 2006 Aug 1;66(11):1203-12. doi: 10.1002/pros.20410.


Background: The PI3K/AKT/mTOR pathway is central to prostate cancer progression. A preliminary investigation of immuno-histochemical expression of mammalian target of rapamycin (mTOR) pathway markers was undertaken to identify patterns of expression in prostate tissue.

Methods: Immunohistochemistry was performed on a custom-made prostate tissue array. Mean long scores and variability of long scores for each marker were recorded for normal lumenal cells, prostate intraepithelial neoplasia (PIN), and cancer.

Results: Expression of PTEN decreased and mTOR signaling pathway markers increased in PIN and in cancer as compared to normal cells in the majority of samples. Overexpression of 4E-BP1 and p-4E-BP1 was observed in PIN and cancer. However, in cancer, the overexpression of 4E-BP1 was significantly higher than with any other marker.

Discussion: Results suggest that 4E-BP1 overexpression is strongly associated with prostate cancer, especially when combined with PTEN and mTOR expression data. Hierarchical clustering analysis utilizing PTEN, mTOR, and 4E-BP1 separated normal from cancer cell populations in most cases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Biomarkers, Tumor / analysis*
  • Cell Cycle Proteins
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Staging
  • PTEN Phosphohydrolase / analysis*
  • Phosphoproteins / analysis*
  • Prostate / chemistry
  • Prostate / pathology
  • Prostatic Intraepithelial Neoplasia / chemistry
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / chemistry*
  • Prostatic Neoplasms / pathology
  • Protein Kinases / analysis
  • Protein Kinases / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases


  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase