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
PPARgamma, a
nuclear hormone receptor important for
lipid and
glucose homeostasis, may present a new therapeutic approach for
breast cancer, since
PPARgamma agonists promote cell cycle arrest, differentiation and apoptosis in
breast cancer cells. Here we determined whether BAG-1 also modulated
PPARgamma function in MCF7 cells. 15-deoxy-Delta12, 14-prostaglandin J(2) (15dPGJ2), an agonistic
ligand for
PPARgamma, 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
PPARgamma-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
PPARgamma function, but the overexpression of BAG-1 in some breast
cancers may limit the efficacy of
PPARgamma agonists as
cancer therapies, by suppression of
PPARgamma-induced cell death pathways.