Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Academic Article uri icon

Overview

abstract

  • The recently identified PTEN/MMAC1 gene is a candidate tumor suppressor implicated in multiple tumor types based on mutations or homozygous deletions of the gene in certain human cancers. No studies of PTEN/MMAC1 mRNA or protein expression in cancer cells have been reported, primarily because of significant numbers of normal cells contaminating most tumor samples and because of the lack of antibody reagents. We examined PTEN/MMAC1 in advanced prostate cancer for gene mutations or abnormalities in expression by using a series of recently derived xenografts free of normal human cells and a PTEN/MMAC1-specific antibody. Only 1 of 10 tumors contained a homozygous deletion of PTEN/MMAC1, and no mutations were detected in the entire coding region of the remaining nine xenografts. However, five of these showed reduced or absent PTEN/MMAC1 expression by Northern analysis and reverse transcription-PCR of mRNA. PTEN/MMAC1 mRNA expression was restored in nonexpressing prostate cancer cells by in vitro treatment with the demethylating agent 5-azadeoxycytidine. Alterations in PTEN/MMAC1 expression were confirmed at the protein level by immunoblot analysis, and immunohistochemical studies show that the endogenous wild-type PTEN/MMAC1 protein is localized exclusively in the cytoplasm. These results demonstrate that loss of PTEN/MMAC1 expression occurs frequently in advanced prostate cancer.

publication date

  • April 28, 1998

Research

keywords

  • Genes, Tumor Suppressor
  • Phosphoric Monoester Hydrolases
  • Prostatic Neoplasms
  • Protein Tyrosine Phosphatases
  • Tumor Suppressor Proteins

Identity

PubMed Central ID

  • PMC20246

Scopus Document Identifier

  • 0032574718

Digital Object Identifier (DOI)

  • 10.1073/pnas.95.9.5246

PubMed ID

  • 9560261

Additional Document Info

volume

  • 95

issue

  • 9