BAG-1 expression and function in breast cancer
BAG-1 expression and function in breast cancer
BAG-1 is a multifunctional protein that binds a wide range of cellular targets including heat shock proteins and some nuclear hormone receptors. BAG-1 exists as three isoforms, BAG-1L, BAG-1M and BAG-IS. BAG-1L contains a nuclear localisation signal, which is not present in the other isoforms and is predominantly localised in the cell nucleus.
To determine the significance of BAG-1 expression in breast cancer, tumours from 138 patients with breast cancer treated with hormonal therapy were analysed by immunohistochemistry. Nuclear BAG-1 immunostaining was associated with expression of oestrogen receptor alpha and progesterone receptor and with improved survival. Reporter gene assays were used to determine the effects of BAG-1 isoforms on oestrogen dependent transcription, and coimmunoprecipitation assays to analyse the interaction of BAG-1 with oestrogen receptors. The nuclear BAG-1 isoform, BAG-1L, interacted with oestrogen receptor alpha and beta and increased oestrogen dependent transcription in breast cancer cells. BAG-IS is also highly expressed in some breast cancers, and to investigate its role in protecting breast cancer cells from apoptosis reporter assays and microarray analysis were used. BAG-IS overexpression reduced p53 dependent transcription and candidate BAG-1 target genes that may be involved in protecting breast cancer cells from apoptosis were identified.
BAG-1 protects breast cancer cells from apoptosis and interferes with p53 function. Importantly, since high levels of BAG-1 L can increase responsiveness to oestrogens in breast cancer cells, BAG-1 may be a marker of responsiveness to hormonal therapy, via direct effects on receptor function. These findings support the hypothesis that BAG-1 is an important molecule in breast cancer and suggest that BAG-1 may prove to be a novel target for cancer therapy.
University of Southampton
Cutress, Ramsey Ian
9e601f6d-7334-4bd8-b559-4e3bce42470a
2003
Cutress, Ramsey Ian
9e601f6d-7334-4bd8-b559-4e3bce42470a
Cutress, Ramsey Ian
(2003)
BAG-1 expression and function in breast cancer.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
BAG-1 is a multifunctional protein that binds a wide range of cellular targets including heat shock proteins and some nuclear hormone receptors. BAG-1 exists as three isoforms, BAG-1L, BAG-1M and BAG-IS. BAG-1L contains a nuclear localisation signal, which is not present in the other isoforms and is predominantly localised in the cell nucleus.
To determine the significance of BAG-1 expression in breast cancer, tumours from 138 patients with breast cancer treated with hormonal therapy were analysed by immunohistochemistry. Nuclear BAG-1 immunostaining was associated with expression of oestrogen receptor alpha and progesterone receptor and with improved survival. Reporter gene assays were used to determine the effects of BAG-1 isoforms on oestrogen dependent transcription, and coimmunoprecipitation assays to analyse the interaction of BAG-1 with oestrogen receptors. The nuclear BAG-1 isoform, BAG-1L, interacted with oestrogen receptor alpha and beta and increased oestrogen dependent transcription in breast cancer cells. BAG-IS is also highly expressed in some breast cancers, and to investigate its role in protecting breast cancer cells from apoptosis reporter assays and microarray analysis were used. BAG-IS overexpression reduced p53 dependent transcription and candidate BAG-1 target genes that may be involved in protecting breast cancer cells from apoptosis were identified.
BAG-1 protects breast cancer cells from apoptosis and interferes with p53 function. Importantly, since high levels of BAG-1 L can increase responsiveness to oestrogens in breast cancer cells, BAG-1 may be a marker of responsiveness to hormonal therapy, via direct effects on receptor function. These findings support the hypothesis that BAG-1 is an important molecule in breast cancer and suggest that BAG-1 may prove to be a novel target for cancer therapy.
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Published date: 2003
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Local EPrints ID: 465101
URI: http://eprints.soton.ac.uk/id/eprint/465101
PURE UUID: d84bfcf4-e4b3-4dfc-b6f4-f3f0201476ad
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Date deposited: 05 Jul 2022 00:23
Last modified: 16 Mar 2024 19:57
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Author:
Ramsey Ian Cutress
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