Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma

Hum Pathol. 1999 Apr;30(4):419-24. doi: 10.1016/s0046-8177(99)90117-x.

Abstract

The PTEN tumor suppressor gene encodes a dual-specificity protein phosphatase that may play a key role in modulating integrin-mediated signals. Inactivation of the PTEN gene has been detected in a small percentage of clinically localized prostate cancers but is common in metastatic disease. It has been shown in glioblastoma cell lines that loss of chromosome 10q, where the PTEN gene is located, is associated with increased angiogenic activity in the conditioned medium attributable to downregulation of thrombospondin-1, a negative regulator of angiogenesis. Therefore, we wished to determine whether inactivation of PTEN might be associated with increased angiogenesis in prostate cancers, because increased angiogenesis in localized cancers is associated with development of metastatic disease. Angiogenesis was assessed by counting microvessels in areas of maximal neovascularization after immunostaining with anti-factor VIII-related antigen antibodies in eight cases with proven homozygous deletion of the PTEN gene and 24 control cases. There was a statistically significant correlation between PTEN inactivation and increased microvessel counts. The microvessel density was higher at all Gleason scores in the cases with PTEN inactivation compared with control cases with the same score. To determine whether the increased angiogenesis in cases with PTEN inactivation was caused by downregulation of expression of the angiogenesis inhibitor thrombospondin-1, we analyzed a subset of the cases by immunostaining with anti-thrombospondin-1 antibody. Approximately 25% of cases showed decreased staining of prostate cancer cells, but there was no correlation with PTEN inactivation. Thus, PTEN inactivation is associated with increased angiogenesis, but the increased angiogenesis is not attributable to downregulation of thrombospondin-1 expression.

Publication types

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

MeSH terms

  • Carcinoma / blood supply*
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Immunohistochemistry
  • Male
  • Neovascularization, Pathologic / genetics*
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / physiology*
  • Prostatic Neoplasms / blood supply*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Thrombospondin 1 / biosynthesis
  • Tumor Suppressor Proteins*

Substances

  • Thrombospondin 1
  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human