Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation

Cancer Res. 2001 Feb 1;61(3):921-5.

Abstract

We analyzed Wilms' tumor suppressor 1 (WT1) expression and its regulation by promoter methylation in a panel of normal breast epithelial samples and primary carcinomas. Contrary to previous reports, WT1 protein was strongly expressed in primary carcinomas (27 of 31 tumors) but not in normal breast epithelium (1 of 20 samples). Additionally, the WT1 promoter was methylated in 6 of 19 (32%) primary tumors, which nevertheless expressed WT1. The promoter is not methylated in normal epithelium. Thus, although tumor-specific methylation of WT1 is established in primary breast cancer at a low frequency, other transcriptional regulatory mechanisms appear to supercede its effects in these tumors. Our results demonstrate expression of WT1 in mammary neoplasia, and that WT1 may not have a tumor suppressor role in breast cancer.

Publication types

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

MeSH terms

  • Breast / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Line
  • Cell Line, Transformed
  • CpG Islands
  • DNA Methylation*
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Epithelium / metabolism
  • Female
  • Gene Expression
  • Genes, Wilms Tumor / genetics*
  • Humans
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Tumor Cells, Cultured
  • WT1 Proteins

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • Transcription Factors
  • WT1 Proteins