Correlation between loss of PTEN expression and Akt phosphorylation in endometrial carcinoma

Clin Cancer Res. 2001 Apr;7(4):892-5.

Abstract

The tumor suppressor PTEN acts as a lipid phosphatase, regulates the phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway, and modulates cell cycle progression and cell survival. Somatic mutations of PTEN have been reported in a variety of cancers, especially in endometrial carcinoma. To clarify whether and how PTEN and the PI3K/Akt pathway relates to endometrial carcinoma, we examined the expression of those pathway-related proteins in patients with endometrial carcinoma. Of 103 endometrial carcinomas, 37 (36%) showed negative immunohistochemical staining of PTEN. Western blotting revealed that the expression of PTEN in PTEN-negative cases was significantly lower compared with that in positive cases. In contrast, phospho-Akt level in negative cases was significantly higher. We found a significant inverse correlation between PTEN and phospho-Akt (r = -0.796). The expression of phospho-Bad was greater in negative cases, suggesting that Bad might be a target for AKT: The present study demonstrates the phosphorylation of Akt accompanied by the loss of PTEN in clinical specimens of endometrial carcinomas.

MeSH terms

  • Carrier Proteins / metabolism
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Female
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphorylation
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Statistics as Topic
  • Tumor Suppressor Proteins*
  • bcl-Associated Death Protein

Substances

  • BAD protein, human
  • Carrier Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • bcl-Associated Death Protein
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human