Expression of E-cadherin transcriptional regulators in ovarian carcinoma

Virchows Arch. 2006 Nov;449(5):520-8. doi: 10.1007/s00428-006-0274-6. Epub 2006 Oct 6.

Abstract

Unlike most epithelial cancers, E-cadherin expression is upregulated in ovarian carcinoma effusions compared with corresponding primary tumors. In the present study, we analyzed the anatomic site-specific expression of transcription factors that negatively regulate E-cadherin in ovarian carcinoma. Using reverse-transcription polymerase chain reaction, mRNA in situ hybridization, and Western blotting, we analyzed the expression and localization of the Snail, Slug, and SIP1 transcription factors and E-cadherin in 78 effusions, 41 primary carcinomas, and 15 solid metastases. Slug mRNA and protein expression was highest in metastases (p=0.042 and p<0.001, respectively). Snail mRNA was comparable at all anatomic sites, but higher protein expression was found in primary tumors and solid metastases compared with effusions (p<0.001). SIP1 mRNA expression was higher in effusions (p<0.001) compared to other sites. Confocal microscopy analysis of fresh and cultured cells from effusion specimens revealed cytoplasmic localization of the Snail protein in primary tumor cells, with a nuclear shift following culturing of these cells. In conclusion, E-cadherin and its negative regulators show site-dependent expression in ovarian carcinoma. In solid tumors, E-cadherin is negatively regulated by Snail and Slug. In effusions, SIP1 may be the main regulator of E-cadherin, but with a lesser level of suppression compared with primary tumors and solid metastases.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Cadherins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization
  • Middle Aged
  • Molecular Sequence Data
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / genetics
  • Ovarian Neoplasms / metabolism*
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / genetics
  • Repressor Proteins / genetics
  • Snail Family Transcription Factors
  • Transcription Factors / analysis
  • Transcription Factors / genetics

Substances

  • Cadherins
  • GEMIN2 protein, human
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors