Dynamics of estrogen-induced ROS and DNA strand break generation in estrogen receptor α-positive breast cancer

Biochem Biophys Res Commun. 2022 Apr 30:602:170-178. doi: 10.1016/j.bbrc.2022.02.089. Epub 2022 Mar 1.

Abstract

DNA repair machinery is involved in estrogen-dependent transactivation. Mounting evidence suggests that mechanisms underlying estrogen-induced DNA damage are complicated. To date estrogen-induced DNA oxidation and its impact on ERα-mediated transaction remains ambiguous. Herein, we found that the process of 17β-estradiol (E2)-induced ROS production can be approximately divided into two phases according to responding time and generation mechanisms. The intracellular Ca2+ fluctuation and ERα-dependent transcription lead to temporospatially different oxidative DNA damage. Further, we demonstrate that DNA oxidation is dispensable for estrogen-responsive gene expression. Dynamics of estrogen-induced DNA strand break generation also show two-phase pattern and topoisomerase-mediated DNA stand breaks are essential in estrogen signaling. Collectively, our findings have provided new insights into oxidative DNA damage in estrogen signaling.

Keywords: DNA oxidation; DNA strand breaks; Estrogen signaling; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • DNA
  • DNA Damage
  • Estradiol / metabolism
  • Estrogen Receptor alpha* / metabolism
  • Estrogens / pharmacology
  • Female
  • Humans
  • Reactive Oxygen Species / metabolism

Substances

  • Estrogen Receptor alpha
  • Estrogens
  • Reactive Oxygen Species
  • Estradiol
  • DNA