Peroxisome proliferator-activated receptor gamma overexpression and knockdown: impact on human B cell lymphoma...

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a multifunctional transcription factor that regulates adipogenesis, immunity and inflammation. Our laboratory previously demonstrated that PPARgamma ligands induce apoptosis in malignant B cells. While malignant B lineage cells such as B cell lymphoma express PPARgamma, its physiological function remains unknown. Herein, we demonstrate that silencing PPARgamma expression by RNAi in human Burkitt's type B lymphoma cells increased basal and mitogen-induced proliferation and survival, which was accompanied by enhanced NF-kappaB activity and increased expression of Bcl-2. These cells also had increased survival upon exposure to PPARgamma ligands and exhibited a less differentiated phenotype. In contrast, PPARgamma overexpression in B lymphoma cells inhibited cell growth and decreased their proliferative response to mitogenic stimuli. These cells were also more sensitive to PPARgamma-ligand induced growth arrest and displayed a more differentiated phenotype. Collectively, these findings support a regulatory role for PPARgamma in the proliferation, survival and differentiation of malignant B cells. These findings further suggest the potential of PPARgamma as a therapeutic target for B cell malignancy.