Unknown

Dataset Information

0

Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen.


ABSTRACT: Crosstalk between the oestrogen receptor (ER) and ERBB2/HER-2 pathways has long been implicated in breast cancer aetiology and drug response, yet no direct connection at a transcriptional level has been shown. Here we show that oestrogen-ER and tamoxifen-ER complexes directly repress ERBB2 transcription by means of a cis-regulatory element within the ERBB2 gene in human cell lines. We implicate the paired box 2 gene product (PAX2), in a previously unrecognized role, as a crucial mediator of ER repression of ERBB2 by the anti-cancer drug tamoxifen. We show that PAX2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ERBB2 transcription, the outcome of which determines tamoxifen response in breast cancer cells. The repression of ERBB2 by ER-PAX2 links these two breast cancer subtypes and suggests that aggressive ERBB2-positive tumours can originate from ER-positive luminal tumours by circumventing this repressive mechanism. These data provide mechanistic insight into the molecular basis of endocrine resistance in breast cancer.

SUBMITTER: Hurtado A 

PROVIDER: S-EPMC2920208 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


Crosstalk between the oestrogen receptor (ER) and ERBB2/HER-2 pathways has long been implicated in breast cancer aetiology and drug response, yet no direct connection at a transcriptional level has been shown. Here we show that oestrogen-ER and tamoxifen-ER complexes directly repress ERBB2 transcription by means of a cis-regulatory element within the ERBB2 gene in human cell lines. We implicate the paired box 2 gene product (PAX2), in a previously unrecognized role, as a crucial mediator of ER r  ...[more]

Similar Datasets

| S-EPMC5520704 | biostudies-literature
| S-EPMC4742586 | biostudies-literature
| S-EPMC2361404 | biostudies-literature
| S-EPMC5566515 | biostudies-literature
| S-EPMC3718507 | biostudies-literature
| S-EPMC2816645 | biostudies-literature
| S-EPMC9427858 | biostudies-literature
| S-EPMC1216893 | biostudies-other
| S-EPMC7174880 | biostudies-literature
| S-EPMC2376286 | biostudies-literature