The University of Southampton
University of Southampton Institutional Repository

The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells

The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells
The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells
Estrogen receptor-? (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer.
0167-6806
Thiruchelvam, Paul T. R.
ff5c3050-60ae-4c0d-91cb-fe0006b019c6
Lai, Chun-Fui
03d817a9-2869-4025-9564-293bbb3e6e7b
Hua, Hui
3096377f-caf1-4c31-8d60-6765da690519
Thomas, Ross S.
c94dfa9e-66a7-45e3-a0ba-f12c28661c0a
Hurtado, Antoni
dd316c6c-5787-4edc-b157-aa7adc125ab5
Hudson, William
150662ab-5f6d-4545-b009-77ab500016a9
Bayly, Andrew R.
c775d71d-87fb-4015-aa5a-13f09e2abf5e
Kyle, Fiona J.
fd92fbe0-7f02-4ebe-bc67-a11fe98cb454
Periyasamy, Manikandan
3a84a6c0-4e0f-47da-ada8-00d4d3c3d667
Photiou, Andrew
e433a7ad-eaed-4a2f-bf30-5b5821774370
Spivey, Alan C.
05a4bbba-1f4c-4950-b9bd-6f4e33c898a5
Ortlund, Eric A.
e2816623-430b-4a99-9413-8c1ca2e098f1
Whitby, Richard J.
45632236-ab00-4ad0-a02d-6209043e818b
Carroll, Jason S.
a94b37bd-6a58-45f6-84fd-90d369e520a1
Coombes, R. Charles
12fc9313-bfc4-48c5-ad76-85d4323123ef
Buluwela, Laki
ab1a78c9-2f88-4152-bcd3-04332014f04c
Ali, Simak
7d471c65-fb89-4edb-be44-965f39215a85
Thiruchelvam, Paul T. R.
ff5c3050-60ae-4c0d-91cb-fe0006b019c6
Lai, Chun-Fui
03d817a9-2869-4025-9564-293bbb3e6e7b
Hua, Hui
3096377f-caf1-4c31-8d60-6765da690519
Thomas, Ross S.
c94dfa9e-66a7-45e3-a0ba-f12c28661c0a
Hurtado, Antoni
dd316c6c-5787-4edc-b157-aa7adc125ab5
Hudson, William
150662ab-5f6d-4545-b009-77ab500016a9
Bayly, Andrew R.
c775d71d-87fb-4015-aa5a-13f09e2abf5e
Kyle, Fiona J.
fd92fbe0-7f02-4ebe-bc67-a11fe98cb454
Periyasamy, Manikandan
3a84a6c0-4e0f-47da-ada8-00d4d3c3d667
Photiou, Andrew
e433a7ad-eaed-4a2f-bf30-5b5821774370
Spivey, Alan C.
05a4bbba-1f4c-4950-b9bd-6f4e33c898a5
Ortlund, Eric A.
e2816623-430b-4a99-9413-8c1ca2e098f1
Whitby, Richard J.
45632236-ab00-4ad0-a02d-6209043e818b
Carroll, Jason S.
a94b37bd-6a58-45f6-84fd-90d369e520a1
Coombes, R. Charles
12fc9313-bfc4-48c5-ad76-85d4323123ef
Buluwela, Laki
ab1a78c9-2f88-4152-bcd3-04332014f04c
Ali, Simak
7d471c65-fb89-4edb-be44-965f39215a85

Thiruchelvam, Paul T. R., Lai, Chun-Fui, Hua, Hui, Thomas, Ross S., Hurtado, Antoni, Hudson, William, Bayly, Andrew R., Kyle, Fiona J., Periyasamy, Manikandan, Photiou, Andrew, Spivey, Alan C., Ortlund, Eric A., Whitby, Richard J., Carroll, Jason S., Coombes, R. Charles, Buluwela, Laki and Ali, Simak (2010) The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells. Breast Cancer Research and Treatment. (doi:10.1007/s10549-010-0994-9). (PMID:20607599)

Record type: Article

Abstract

Estrogen receptor-? (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer.

Full text not available from this repository.

More information

Published date: 2010

Identifiers

Local EPrints ID: 176819
URI: http://eprints.soton.ac.uk/id/eprint/176819
ISSN: 0167-6806
PURE UUID: a059b3fb-0ee9-4bec-81da-1d04512e2da0
ORCID for Richard J. Whitby: ORCID iD orcid.org/0000-0002-9891-5502

Catalogue record

Date deposited: 11 Mar 2011 11:23
Last modified: 05 Nov 2019 02:09

Export record

Altmetrics

Contributors

Author: Paul T. R. Thiruchelvam
Author: Chun-Fui Lai
Author: Hui Hua
Author: Ross S. Thomas
Author: Antoni Hurtado
Author: William Hudson
Author: Andrew R. Bayly
Author: Fiona J. Kyle
Author: Manikandan Periyasamy
Author: Andrew Photiou
Author: Alan C. Spivey
Author: Eric A. Ortlund
Author: Jason S. Carroll
Author: R. Charles Coombes
Author: Laki Buluwela
Author: Simak Ali

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×