Peroxisome proliferator-activated receptor gamma overexpression and knockdown: impact on human B cell lymphoma proliferation and survival.
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.
Garcia-Bates
Tatiana M
TM
Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Peslak
Scott A
SA
Baglole
Carolyn J
CJ
Maggirwar
Sanjay B
SB
Bernstein
Steven H
SH
Phipps
Richard P
RP
D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism*; D051757:PAX5 Transcription Factor / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism*
D008024:Ligands; D016328:NF-kappa B; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1