5'-CpG island promoter hypermethylation of the CAV-1 gene in breast cancer patients of Kashmir

Asian Pac J Cancer Prev. 2012;13(1):371-5. doi: 10.7314/apjcp.2012.13.1.371.

Abstract

Background: Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signalling. Aberrant promoter methylation of CAV-1 is associated with inactivation of expression. We previously observed CAV-1 mutations in breast cancers and therefore devised this study to examine the hypermethylation status of the promoter region of CAV-1 with reference to breast cancer progression and development.

Methods: Hypermethylation status of CAV-1 was analyzed by methylation specific PCR. Loss of expression of the CAV-1 gene was further evaluated by semi-quantitative rt-PCR.

Results: 28/130 (21.5%) breast cancer cases showed promoter hypermethylation with reduced CAV-1 expression levels when compared with adjacent normal breast tissue. CAV-1 gene hypermethylation was significantly related to menopausal status, histopathological grade and age.

Conclusion: The rationale of our study is that CAV-1 gene is transcriptionally repressed in breast cancer cells due to hypermethylation. Our results reveal that promoter hypermethylation and loss of expression of the CAV-1 gene is an important alternative mechanism for inactivation of CAV-1 leading to complete gene silencing.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Caveolin 1 / genetics*
  • Cohort Studies
  • CpG Islands / genetics*
  • DNA Methylation*
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • India
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics

Substances

  • CAV1 protein, human
  • Caveolin 1
  • DNA, Neoplasm
  • RNA, Messenger