In Utero Estrogen Exposure Increases Antiestrogen Resistance by Inducing EMT

Abstract

Endocrine therapies such as antiestrogens (AE) are widely used in estrogen receptor positive (ER+) breast cancer, due to their efficacy and limited toxicity. However, the clinical reality is that of the ~50% of ER+ patients that initially respond to these therapies, many will acquire resistance and recur. The causes of antiestrogen resistance are currently unclear. Our recent preclinical study found that maternal exposure to excess estrogens during pregnancy increases the risk that AE resistance in ER+ mammary tumors in the offspring. This increase may be caused by epigenetic mechanisms, such as an increase in DNA methyltransferases (DNMT) and methylation, and histone deacetylases (HDAC) and histone modifications. In this study, our preliminary data show not only an increase in TAM resistance in rats exposed to in utero estrogen, but concurrent treatment with DNMT and HDAC inhibitors inhibited this resistance, suggesting that epigenetic changes driven by estrogenic exposures early in life may preprogram the breast to develop tumors with a higher propensity to develop antiestrogen resistance.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2015
Accession Number
ADA615228

Entities

People

  • Kerrie B. Bouker

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Alkynes
  • Biology
  • Biomedical Research
  • Breast Cancer
  • Chemistry
  • Computational Biology
  • Department Of Defense
  • Enzyme Inhibitors
  • Estrogens
  • Inhibitors
  • Mammary Glands
  • Medical Personnel
  • Neoplasms
  • Proteins
  • Students
  • Systems Biology
  • Training

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Biology and Genetics
  • Oncology