Garcia-Bates Tatiana M, Peslak Scott A, Baglole Carolyn J, Maggirwar Sanjay B, Bernstein Steven H, Phipps Richard P
Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Cancer Immunol Immunother. 2009 Jul;58(7):1071-83. doi: 10.1007/s00262-008-0625-z. Epub 2008 Nov 19.
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.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种多功能转录因子，可调节脂肪生成、免疫和炎症。我们实验室先前证明，PPARγ配体可诱导恶性B细胞凋亡。虽然恶性B谱系细胞如B细胞淋巴瘤表达PPARγ，但其生理功能仍不清楚。在此，我们证明，通过RNA干扰沉默人伯基特氏B型淋巴瘤细胞中的PPARγ表达可增加基础增殖和有丝分裂原诱导的增殖及存活，这伴随着增强的核因子κB活性和Bcl-2表达增加。这些细胞在暴露于PPARγ配体时也有更高的存活率，并表现出分化程度较低的表型。相反，B淋巴瘤细胞中PPARγ的过表达抑制细胞生长，并降低其对有丝分裂原刺激的增殖反应。这些细胞对PPARγ配体诱导的生长停滞也更敏感，并表现出更分化的表型。总的来说，这些发现支持PPARγ在恶性B细胞的增殖、存活和分化中起调节作用。这些发现进一步表明PPARγ作为B细胞恶性肿瘤治疗靶点的潜力。
