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

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