c-Jun/AP-1 overexpression reprograms ERα signaling related to tamoxifen response in ERα-positive breast cancer.

Oncogene
Huan HeKarin Dahlman-Wright

Abstract

A critical mechanism that has been proposed for transcription regulation by estrogen receptor α (ER) is the tethering of ER to DNA via other transcription factors, such as AP-1. However, genome-wide assessment of the overlap in chromatin binding repertoires of these two transcription factors has not been reported. Here, we show that the AP-1 transcription factor c-Jun interacts with ER and that c-Jun chromatin binding shows extensive overlap with ER binding at the global level. Further, we show that c-Jun overexpression reprograms ER chromatin binding and modulates ER-mediated gene regulation. Our data are consistent with a mechanism where estrogen/ER-dependent crosstalk with AP-1 at the transcriptional level is mediated through the tethering of ER to DNA bound AP-1. Additionally, in our system c-Jun overexpression causes reduced sensitivity to tamoxifen in ER+ breast cancer cells. Integrated cistrome, transcriptome, and clinical data reveal TGFBI as a candidate gene which may confer tamoxifen resistance by ER and AP-1 crosstalk. Further, we show that TGFBI expression is elevated in breast cancer compared to normal breast. Together, our data provide a novel genome-wide footprint of ER and AP-1 crosstalk and suggest AP-1 and TGF...Continue Reading

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Citations

Apr 13, 2018·Nucleic Acids Research·Wendy N JeffersonCarmen J Williams
Mar 3, 2021·Cancer Letters·Dandan SongCecilia Williams
Dec 29, 2020·Molecular Aspects of Medicine·Isabel Mayayo-PeraltaWilbert Zwart
May 4, 2021·Cellular Signalling·Armando Corona, Gerard C Blobe
Aug 18, 2021·Nucleic Acids Research·Athena SkliasZdenko Herceg

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Datasets Mentioned

BETA
GSE102412

Methods Mentioned

BETA
xenograft
immunoprecipitation
co-immunoprecipitation
ChIP-seq
transfection

Software Mentioned

DAVID
JAVA Tree View
ImageJ
Cluster
HOMER
KMplot
Qlucore Omics Explorer ( QOE )
Cistrome
Affymetrix Transcriptome Analysis Console ( TAC )

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