Breast cancer upregulating genes in stromal cells by LINE-1 hypermethylation and micrometastatic detection

Epigenomics. 2016 Apr;8(4):475-86. doi: 10.2217/epi-2015-0007. Epub 2016 Apr 1.

Abstract

Changes in the methylation level of genes containing LINE-1 alter host gene regulation.

Aim: This study demonstrates that paracrine signaling of breast cancer influences the epigenetic regulation of stromal cells.

Methods: We proved in vitro and in vivo breast cancer promoted LINE-1 methylation exists exclusively in female stromal cells.

Results: Genes containing LINE-1 of breast cancer stromal cells were upregulated. Furthermore, one of the genes, MUC-1, was demonstrated to have expression in plasma cells from the lymph nodes of patients with lymph node metastasis or micrometastasis.

Conclusion: Breast cancer sends a paracrine signal to stroma cells causing LINE-1 epigenetic regulation. Moreover, the regulated genes in stroma cells are potential biomarkers for detecting breast cancer micrometastasis.

Keywords: LINE-1 hypermethylation; breast cancer; tumor supporting tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Long Interspersed Nucleotide Elements*
  • Lymphatic Metastasis
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Neoplasm Micrometastasis / genetics
  • Paracrine Communication*
  • Stromal Cells / metabolism*
  • Up-Regulation

Substances

  • MUC1 protein, human
  • Mucin-1