RDM1 promotes critical processes in breast cancer tumorigenesis

J Cell Mol Med. 2019 Aug;23(8):5432-5439. doi: 10.1111/jcmm.14425. Epub 2019 Jun 20.

Abstract

Breast cancer is currently among the most common cancers in women, with almost 200,000 new cases diagnosed annually. Dysregulation of DNA repair pathways allows cells to accumulate damage and eventually mutations, with a subsequent reduction in DNA repair capacity in breast tissue, leading to tumorigenesis. One component of the DNA damage repair pathway is RAD52 motif-containing 1 (RDM1), but the specific role of RDM1 in breast cancer and the underlying mechanism remain unclear. Here, we examined the role played by RDM1 in breast cancer cell culture using the HBL100 and MCF-7 breast cancer cell lines. Disruption of RDM1 reduced in vitro cell proliferation and promoted apoptosis. Knockdown of RDM1 also induced up-regulation of p53 levels, whereas RAD51 and RAD52, both involved in DNA repair, were down-regulated. In addition, the in vivo growth of RDM1-deficient cells was significantly repressed, suggesting that RDM1 is a novel oncogenic protein in human breast cancer cells. This study reveals a link between the DNA damage response pathway and oncogenic functionality in breast cancer. Accordingly, therapeutic targeting of RDM1 is a potential treatment strategy for breast cancer and overcoming drug resistance.

Keywords: DNA damage repair; RDM1; oncogenic protein.

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA Damage / genetics
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Down-Regulation / genetics
  • Female
  • Humans
  • MCF-7 Cells
  • Mutation / genetics
  • Up-Regulation / genetics

Substances

  • DNA-Binding Proteins
  • RDM1 protein, human