BASP1 interacts with oestrogen receptor \u03b1 and modifies the tamoxifen response

Lindsey A Marsh,Kate J Heesom,Kathryn F Medler,Stefan Ge Roberts,Andrew D Davidson,Samantha Carrera,Jayasha Shandilya

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.

Highlights

BASP1 was originally identified as a membrane and cytoplasmic protein that sequesters lipids through an N-terminal myristoyl motif.[1]
We have demonstrated that BASP1 can act as a transcriptional corepressor of ERα
BASP1 is recruited to the promoter regions of ERα target genes and its functional interaction is enhanced by the treatment of cells with tamoxifen

Summary

Introduction

BASP1 was originally identified as a membrane and cytoplasmic protein that sequesters lipids through an N-terminal myristoyl motif.[1] BASP1 is present in the nucleus and can function as a transcriptional corepressor for the Wilms’ tumour 1 protein WT1.2 BASP1 is recruited to the gene promoter by WT1 and converts WT1 from a transcriptional activator to a repressor. The inhibitory effect of BASP1 on WT1 transcription function is consistent with this notion because WT1 can act as an oncogene in many adult cancers.[10] The widespread expression of BASP1 suggests that its transcriptional repressor activities are likely to be used by other DNA-. Many breast cancers can present tamoxifen resistance and several studies have identified the gene expression changes that accompany this resistance but the underlying reasons are still not clear.[12,13,14,15,16]. BASP1 is expressed in breast cancer tissue and is associated with enhanced survival

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Conclusion