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

  • Authors:
    • Simon J. Crabb
    • Angela Hague
    • Peter W.M. Johnson
    • Graham Packham
  • View Affiliations

  • Published online on: March 1, 2008     https://doi.org/10.3892/or.19.3.689
  • Pages: 689-696
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

March 2008
Volume 19 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Crabb SJ, Hague A, Johnson PW and Packham G: BAG-1 inhibits PPARγ-induced cell death, but not PPARγ-induced transcription, cell cycle arrest or differentiation in breast cancer cells. Oncol Rep 19: 689-696, 2008
APA
Crabb, S.J., Hague, A., Johnson, P.W., & Packham, G. (2008). BAG-1 inhibits PPARγ-induced cell death, but not PPARγ-induced transcription, cell cycle arrest or differentiation in breast cancer cells. Oncology Reports, 19, 689-696. https://doi.org/10.3892/or.19.3.689
MLA
Crabb, S. J., Hague, A., Johnson, P. W., Packham, G."BAG-1 inhibits PPARγ-induced cell death, but not PPARγ-induced transcription, cell cycle arrest or differentiation in breast cancer cells". Oncology Reports 19.3 (2008): 689-696.
Chicago
Crabb, S. J., Hague, A., Johnson, P. W., Packham, G."BAG-1 inhibits PPARγ-induced cell death, but not PPARγ-induced transcription, cell cycle arrest or differentiation in breast cancer cells". Oncology Reports 19, no. 3 (2008): 689-696. https://doi.org/10.3892/or.19.3.689