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The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription

The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription
The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription
BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets including heat-shock proteins and some nuclear hormone receptors. BAG-1 exists as three major isoforms, BAG-1L, BAG-1M and BAG-1S. BAG-1L contains a nuclear localization signal, which is not present in the other isoforms, and is predominantly localized in the cell nucleus. Here we have investigated the effects of BAG-1 on function of the oestrogen receptor (ER), a key growth control molecule and target for hormonal therapy in breast cancer. We demonstrate that BAG-1L, but not BAG-1S or BAG-1M, increased oestrogen-dependent transcription in breast cancer cells. BAG-1L interacted with and stimulated the activity of both ER ? and ?. Although BAG-1L and ERs colocalize to the nucleus, fusing BAG-1S to an heterologous nuclear localization sequence was not sufficient to stimulate transcription. Consistent with an important effect on receptor function, nuclear BAG-1 expression in breast cancers was associated with expression of the progesterone receptor, a transcriptional target of ER?, and was associated with improved survival in patients treated with hormonal therapy. These data suggest that BAG-1L is an important determinant of ER function in vitro and in human breast cancer.
bag-1, breast cancer, oestrogen, receptor, hormone therapy, survival
0950-9232
4973-4982
Cutress, Ramsey I.
68ae4f86-e8cf-411f-a335-cdba51797406
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Sharp, Adam
f26a1894-b10f-4864-a314-750628d6c0cc
Maison, Anna
946039f2-a78e-4fbe-9339-d0d6fca3d479
Wood, Lynn
23143476-4a29-49df-8038-7f7b64313f5f
Lee, Ron
3fd79c88-b341-4674-bebc-1da69bf004ed
Brimmell, Matthew
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Mullee, Mark A.
fd3f91c3-5e95-4f56-8d73-260824eeb362
Johnson, Peter W.M.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Royle, Gavin T.
de1fd766-dac6-4cea-ad6b-f6fbf755f3e6
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Cutress, Ramsey I.
68ae4f86-e8cf-411f-a335-cdba51797406
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Sharp, Adam
f26a1894-b10f-4864-a314-750628d6c0cc
Maison, Anna
946039f2-a78e-4fbe-9339-d0d6fca3d479
Wood, Lynn
23143476-4a29-49df-8038-7f7b64313f5f
Lee, Ron
3fd79c88-b341-4674-bebc-1da69bf004ed
Brimmell, Matthew
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Mullee, Mark A.
fd3f91c3-5e95-4f56-8d73-260824eeb362
Johnson, Peter W.M.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Royle, Gavin T.
de1fd766-dac6-4cea-ad6b-f6fbf755f3e6
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394

Cutress, Ramsey I., Townsend, Paul A., Sharp, Adam, Maison, Anna, Wood, Lynn, Lee, Ron, Brimmell, Matthew, Mullee, Mark A., Johnson, Peter W.M., Royle, Gavin T., Bateman, Adrian C. and Packham, Graham (2003) The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription. Oncogene, 22 (32), 4973-4982. (doi:10.1038/sj.onc.1206688). (PMID:12902980)

Record type: Article

Abstract

BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets including heat-shock proteins and some nuclear hormone receptors. BAG-1 exists as three major isoforms, BAG-1L, BAG-1M and BAG-1S. BAG-1L contains a nuclear localization signal, which is not present in the other isoforms, and is predominantly localized in the cell nucleus. Here we have investigated the effects of BAG-1 on function of the oestrogen receptor (ER), a key growth control molecule and target for hormonal therapy in breast cancer. We demonstrate that BAG-1L, but not BAG-1S or BAG-1M, increased oestrogen-dependent transcription in breast cancer cells. BAG-1L interacted with and stimulated the activity of both ER ? and ?. Although BAG-1L and ERs colocalize to the nucleus, fusing BAG-1S to an heterologous nuclear localization sequence was not sufficient to stimulate transcription. Consistent with an important effect on receptor function, nuclear BAG-1 expression in breast cancers was associated with expression of the progesterone receptor, a transcriptional target of ER?, and was associated with improved survival in patients treated with hormonal therapy. These data suggest that BAG-1L is an important determinant of ER function in vitro and in human breast cancer.

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More information

Published date: 2003
Keywords: bag-1, breast cancer, oestrogen, receptor, hormone therapy, survival

Identifiers

Local EPrints ID: 26269
URI: http://eprints.soton.ac.uk/id/eprint/26269
ISSN: 0950-9232
PURE UUID: 003fe815-55c9-4a77-b6e6-fe0b89bb37c3
ORCID for Peter W.M. Johnson: ORCID iD orcid.org/0000-0003-2306-4974
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

Catalogue record

Date deposited: 21 Apr 2006
Last modified: 09 Jan 2022 03:03

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Contributors

Author: Paul A. Townsend
Author: Adam Sharp
Author: Anna Maison
Author: Lynn Wood
Author: Ron Lee
Author: Matthew Brimmell
Author: Mark A. Mullee
Author: Gavin T. Royle
Author: Adrian C. Bateman
Author: Graham Packham ORCID iD

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