Expression of NEDD4-1, a PTEN regulator, in gastric and colorectal carcinomas

APMIS. 2008 Sep;116(9):779-84. doi: 10.1111/j.1600-0463.2008.00999.x.

Abstract

Recent studies have disclosed that NEDD4-1 regulates PTEN activity by ubiquitination. NEDD4-1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4-1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4-1 in PTEN regulation in cancer cells, expression of NEDD4-1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4-1 expression in colorectal and gastric cancer tissues. We investigated NEDD4-1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4-1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4-1. There was no significant association of NEDD4-1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4-1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4-1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4-1 expression may play a role in colorectal and gastric cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / pathology
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology
  • Endosomal Sorting Complexes Required for Transport
  • Humans
  • Immunohistochemistry
  • Nedd4 Ubiquitin Protein Ligases
  • PTEN Phosphohydrolase / metabolism
  • Protein Array Analysis / methods
  • Retrospective Studies
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology
  • Ubiquitin-Protein Ligases / biosynthesis*

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • Ubiquitin-Protein Ligases
  • PTEN Phosphohydrolase