BAG-1 inhibits PPARgamma-induced cell death, but not PPARgamma-induced transcription, cell cycle arrest or differentiation in breast cancer cells
BAG-1 inhibits PPARgamma-induced cell death, but not PPARgamma-induced transcription, cell cycle arrest or differentiation in breast cancer cells
BAG-1 is a pleiotropic protein that exists as multiple isoforms. BAG-1 overexpression in breast cancer is associated with outcome. BAG-1 modulates the function of various nuclear hormone receptors, including the oestrogen receptor, and BAG-1 can influence the in vitro action of anti-hormonal therapies such as cyproterone acetate in prostate cancer. Activation of PPAR gamma, a nuclear hormone receptor important for lipid and glucose homeostasis, may present a new therapeutic approach for breast cancer, since PPAR gamma agonists promote cell cycle arrest, differentiation and apoptosis in breast cancer cells. Here we determined whether BAG-1 also modulated PPAR gamma function in MCF7 cells. 15-deoxy-Delta12, 14-prostaglandin J(2) (15dPGJ(2)), an agonistic ligand for PPAR gamma, induced expression of HSP70, a BAG-1 binding partner, but did not alter BAG-1 isoform expression. Overexpression of BAG-1 isoforms did not alter PPAR gamma-dependent transcription or interfere with 15dPGJ(2)-induced cell cycle arrest or differentiation. However, overexpression of BAG-1 isoforms did interfere with induction of cell death by 15dPGJ(2). Thus, BAG-1 is unlikely to directly modulate PPAR gamma function, but the overexpression of BAG-1 in some breast cancers may limit the efficacy of PPAR gamma agonists as cancer therapies, by suppression of PPAR gamma-induced cell death pathways.
apoptosis, 15dPGJ2, BAG-1, breast cancer, heat shock
protein, oestrogen receptor, PPAR?, vitamin d receptor
689-696
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Hague, Angela
0e1199e4-08c3-4e8b-b40f-2fc61555e6f4
Johnson, Peter W.M.
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Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
March 2008
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Hague, Angela
0e1199e4-08c3-4e8b-b40f-2fc61555e6f4
Johnson, Peter W.M.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Crabb, Simon J., Hague, Angela, Johnson, Peter W.M. and Packham, Graham
(2008)
BAG-1 inhibits PPARgamma-induced cell death, but not PPARgamma-induced transcription, cell cycle arrest or differentiation in breast cancer cells.
Oncology Reports, 19 (3), .
Abstract
BAG-1 is a pleiotropic protein that exists as multiple isoforms. BAG-1 overexpression in breast cancer is associated with outcome. BAG-1 modulates the function of various nuclear hormone receptors, including the oestrogen receptor, and BAG-1 can influence the in vitro action of anti-hormonal therapies such as cyproterone acetate in prostate cancer. Activation of PPAR gamma, a nuclear hormone receptor important for lipid and glucose homeostasis, may present a new therapeutic approach for breast cancer, since PPAR gamma agonists promote cell cycle arrest, differentiation and apoptosis in breast cancer cells. Here we determined whether BAG-1 also modulated PPAR gamma function in MCF7 cells. 15-deoxy-Delta12, 14-prostaglandin J(2) (15dPGJ(2)), an agonistic ligand for PPAR gamma, induced expression of HSP70, a BAG-1 binding partner, but did not alter BAG-1 isoform expression. Overexpression of BAG-1 isoforms did not alter PPAR gamma-dependent transcription or interfere with 15dPGJ(2)-induced cell cycle arrest or differentiation. However, overexpression of BAG-1 isoforms did interfere with induction of cell death by 15dPGJ(2). Thus, BAG-1 is unlikely to directly modulate PPAR gamma function, but the overexpression of BAG-1 in some breast cancers may limit the efficacy of PPAR gamma agonists as cancer therapies, by suppression of PPAR gamma-induced cell death pathways.
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Published date: March 2008
Keywords:
apoptosis, 15dPGJ2, BAG-1, breast cancer, heat shock
protein, oestrogen receptor, PPAR?, vitamin d receptor
Identifiers
Local EPrints ID: 62711
URI: http://eprints.soton.ac.uk/id/eprint/62711
ISSN: 1021-335X
PURE UUID: 58a163a1-fe71-487b-841b-6602c12e4558
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Date deposited: 16 Apr 2009
Last modified: 23 Jul 2022 01:51
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Author:
Angela Hague
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