Decreased miR-206 expression in BRCA1 wild-type triple-negative breast cancer cells after concomitant treatment with gemcitabine and a Poly(ADP-ribose) polymerase-1 inhibitor

Anticancer Res. 2014 Sep;34(9):4893-7.

Abstract

No targeted-therapy has been established for triple-negative breast cancer accompanied by mutations in breast cancer susceptibility gene1 (BRCA1) mutation. In the present study, using BRCA1 wild-type cells (MDA-MB-231) and BRCA1-mutated cells (MDA-MB-436), we investigated miRNA expression and apoptosis on day 1 after addition of gemcitabine-alone and in combination with poly ADP-ribose polymerase-1 (PARP1) inhibitor. After drug treatment, there were significantly fewer apoptotic BRCA1 wild-type cells than BRCA1-mutated cells. Expression of miRNA-26a, -29b, -100, and -148a increased in BRCA1 wild-type cells exposed to gemcitabine-alone and in combination with the PARP1 inhibitor. The addition of PARP1 inhibitor reduced miR-206 expression in BRCA1 wild-type cells but increased it in BRCA1-mutated cells. It was suggested that miR-206 serves as a target molecule of PARP1 inhibitor combination therapy for BRCA1 wild-type triple-negative breast cancer cells.

Keywords: BRCA1; PARP1; TNBC; breast cancer cells; miRNA.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • BRCA1 Protein / genetics*
  • Cell Line, Tumor
  • Cell Survival
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics*

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • Enzyme Inhibitors
  • MIRN206 microRNA, human
  • MicroRNAs
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Deoxycytidine
  • Gemcitabine