E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumours

Eur J Cancer. 2003 Mar;39(4):517-23. doi: 10.1016/s0959-8049(02)00175-2.

Abstract

A previous study showed E-cadherin expression was lost in some cervical cancer cell lines and tumours. This study was designed to clarify the significance of DNA methylation in silencing E-cadherin expression. We examined promoter methylation of E-cadherin in five cervical cancer cell lines and 20 cervical cancer tissues using methylation-specific PCR (MSP) and bisulphite DNA sequencing. The correlation of E-cadherin methylation and expression together with methyltransferase (DNMT1) were further studied. We found that hypermethylation of E-cadherin was involved in five cervical cancer cell lines and 40% (8/20) of cervical cancer tissues. E-cadherin protein was lost in 6/8 (75%) samples and 3/5 (60%) cell lines with promoter methylation. E-cadherin methylation was significantly correlated with increased DNMT1. Using an antisense DNMT1 oligo to transfect into SiHa HeLa C33A cell line, E-cadherin protein was re-expressed. We concluded that loss of E-cadherin expression was in part correlated with DNA methylation and DNMT1 expression in cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use
  • Azacitidine / analogs & derivatives*
  • Azacitidine / therapeutic use
  • Blotting, Western
  • Cadherins / metabolism*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • Decitabine
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Molecular Sequence Data
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • Antimetabolites, Antineoplastic
  • Cadherins
  • Enzyme Inhibitors
  • RNA, Messenger
  • RNA, Neoplasm
  • Decitabine
  • DNA (Cytosine-5-)-Methyltransferases
  • Azacitidine