Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G2/M checkpoint signaling

Christoforos G. Thomas, Anders Strom, Karolina Lindberg, Jan-Ake Gustafsson

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Estrogen receptor beta (ERβ) inhibits proliferation in different cellular systems by regulating components of the cell cycle machinery. Eukaryotic cells respond to DNA damage by arresting in G1, S, or G2 phases of the cell cycle to initiate DNA repair. Most tumor cells due to disruptions in the p53-dependent G1 pathway are dependent on S-phase and G2/M checkpoints to maintain genomic integrity in response to DNA damage. We report that induction of ERβ expression causes abrogation of the S-phase, and the Chk1/Cdc25C-mediated G2/M checkpoints after cisplatin and doxorubicin exposure in p53-defective breast cancer cells but not in p53 wild-type mammary cells. This impairment of DNA damage response that involves BRCA1 downregulation and caspase-2 activation results in mitotic catastrophe and decreased cancer cell survival. These results indicate that in cancers where p53 is defective, assessment of the presence of ERβ may be of predictive value for the successful response to chemotherapy.

Original languageEnglish (US)
Pages (from-to)417-427
Number of pages11
JournalBreast Cancer Research and Treatment
Volume127
Issue number2
DOIs
StatePublished - Jun 1 2011

Keywords

  • BRCA1
  • Cancer cells
  • Caspase-2
  • DNA damage response
  • Estrogen receptor beta
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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