Tamoxifen epigenetically modulates CXCL12 expression in MCF-7 breast cancer cells

Biomed Pharmacother. 2010 Jan;64(1):54-7. doi: 10.1016/j.biopha.2009.04.041. Epub 2009 Sep 2.

Abstract

The CXCL12 chemokine binds to the CXCR4 receptor and contributes to survival, proliferation, and migration of malignant cells. Recent reports indicate that breast cancer cells lacking expression of CXCL12 but exhibiting CXCR4 can metastasize to target organs that secrete CXCL12. We observed that Tamoxifen (Tam), similarly to 5-dAzaC, results in significantly increased levels of CXCL12 transcript and protein in MCF-7 breast cancer cells. Bisulfite sequencing suggests that Tam, similarly to 5-dAzaC, may increase CXCL12 expression via reduction in methylation of cytosine in the cytosine-guanosine (CpG) dinucleotide island of the CXCL12 promoter of MCF-7 cells. Our results, together with findings of other researches, may suggest that Tam epigenetically activates CXCL12 expression in breast cancer cells and can make these cells less susceptible to attraction by exogenous CXCL12 to metastasis sites.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Chemokine CXCL12 / drug effects*
  • Chemokine CXCL12 / genetics
  • Cytosine / metabolism
  • DNA Methylation / drug effects
  • Decitabine
  • Epigenesis, Genetic / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Sequence Analysis, DNA / methods
  • Tamoxifen / pharmacology*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Hormonal
  • Chemokine CXCL12
  • Tamoxifen
  • Decitabine
  • Cytosine
  • Azacitidine