BASP1 interacts with oestrogen receptor α and modifies the tamoxifen response

Cell Death Dis. 2017 May 11;8(5):e2771. doi: 10.1038/cddis.2017.179.

Abstract

Tamoxifen binds to oestrogen receptor α (ERα) to elicit distinct responses that vary by cell/tissue type and status, but the factors that determine these differential effects are unknown. Here we report that the transcriptional corepressor BASP1 interacts with ERα and in breast cancer cells, this interaction is enhanced by tamoxifen. We find that BASP1 acts as a major selectivity factor in the transcriptional response of breast cancer cells to tamoxifen. In all, 40% of the genes that are regulated by tamoxifen in breast cancer cells are BASP1 dependent, including several genes that are associated with tamoxifen resistance. BASP1 elicits tumour-suppressor activity in breast cancer cells and enhances the antitumourigenic effects of tamoxifen treatment. Moreover, BASP1 is expressed in breast cancer tissue and is associated with increased patient survival. Our data have identified BASP1 as an ERα cofactor that has a central role in the transcriptional and antitumourigenic effects of tamoxifen.

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Estrogen Receptor alpha / biosynthesis*
  • Estrogen Receptor alpha / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • K562 Cells
  • MCF-7 Cells
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics
  • Tamoxifen / pharmacology*
  • Transcription, Genetic / drug effects*

Substances

  • BASP1 protein, human
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Repressor Proteins
  • Tamoxifen