Expression of BAF57 in ovarian cancer cells and drug sensitivity

Cancer Sci. 2015 Apr;106(4):359-66. doi: 10.1111/cas.12612. Epub 2015 Feb 25.

Abstract

The SMARCE1 (SWI / SNF-related, matrix-associated, and actin-dependent regulator of chromatin, subfamily e, member 1) encodes BAF57 protein. Previously, we reported that BAF57 is a predictive marker of endometrial carcinoma. In this study, we investigated BAF57 expression in ovarian cancer cell lines and their sensitivities to cisplatin, doxorubicin, paclitaxel, and 5-fluorouracil. BAF57 expression was strongly correlated with sensitivities to cisplatin, doxorubicin, and 5-fluorouracil in 10 ovarian cancer cell lines. Paclitaxel sensitivity was also correlated with BAF57 expression, but without significance. In A2780 ovarian cancer cells, knockdown of BAF57 using specific siRNA increased cell cycle arrest at G1 phase and the sensitivities to these anticancer agents. cDNA microarray analysis of A2780 cells transfected with BAF57 siRNA showed that 134 genes were positively regulated by BAF57, including ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2) encoding breast cancer resistance protein (BCRP). We confirmed that knockdown of BAF57 decreased BCRP expression in ovarian cancer cells by Western blot analysis, and that ABCG2 gene expression might be regulated transcriptionally. These results suggested that BAF57 is involved in ovarian cancer cell growth and sensitivity to anticancer agents, and that BAF57 may be a target for ovarian cancer therapy.

Keywords: Anticancer agents; BAF57; BCRP; cell cycle; chemotherapy.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / genetics
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Chromosomal Proteins, Non-Histone / biosynthesis
  • Chromosomal Proteins, Non-Histone / genetics*
  • Cisplatin / therapeutic use
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Fluorouracil / therapeutic use
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / therapeutic use
  • RNA Interference
  • RNA, Small Interfering

Substances

  • ABCG1 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • SMARCE1 protein, human
  • Doxorubicin
  • Paclitaxel
  • Cisplatin
  • Fluorouracil