BAG-1 inhibits PPARγ-induced cell death, but not PPARγ-induced transcription, cell cycle arrest or differentiation in breast cancer cells

SJ Crabb, A Hague, PW Johnson, G Packham

Research output: Contribution to journalArticle (Academic Journal)peer-review

11 Citations (Scopus)

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 PPARγ, a nuclear hormone receptor important for lipid and glucose homeostasis, may present a new therapeutic approach for breast cancer, since PPARγ agonists promote cell cycle arrest, differentiation and apoptosis in breast cancer cells. Here we determined whether BAG-1 also modulated PPARγ function in MCF7 cells. 15-deoxy-Delta12, 14-prostaglandin J(2) (15dPGJ2), an agonistic ligand for PPARγ, 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 PPARγ-dependent transcription or interfere with 15dPGJ2-induced cell cycle arrest or differentiation. However, overexpression of BAG-1 isoforms did interfere with induction of cell death by 15dPGJ2. Thus, BAG-1 is unlikely to directly modulate PPARγ function, but the overexpression of BAG-1 in some breast cancers may limit the efficacy of PPARγ agonists as cancer therapies, by suppression of PPARγ-induced cell death pathways.
Translated title of the contributionBAG-1 inhibits PPARγ-induced cell death, but not PPARγ-induced transcription, cell cycle arrest or differentiation in breast cancer cells
Original languageEnglish
Pages (from-to)689 - 696
Number of pages8
JournalOncology Reports
Volume19 (3)
Publication statusPublished - Mar 2008

Bibliographical note

Publisher: University of Crete Faculty of Medicine

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