Salgia Meghan M, Elix Catherine C, Pal Sumanta K, Jones Jeremy O
Department of Medical Oncology, City of Hope 1500 East Duarte Road, Duarte, CA, USA.
Am J Clin Exp Urol. 2019 Jun 15;7(3):98-109. eCollection 2019.
Due to the increasing occurrence of and high costs associated with prostate cancer (PC), there is an urgent need to develop novel PC treatment and chemoprevention strategies. Although androgen receptor (AR) signaling is significant in the development and progression of PC, other molecular pathways contribute as well. Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) has recently been implicated as an oncogene in PC, which may influence both the development and metastatic progression of the cancer. There are two isoforms of PPARγ, with PPARγ2 having an additional 30 amino acids at the amino terminus. Here, we investigated the differential expression and function of these two isoforms in benign and cancerous prostate epithelial cells. The findings from our immunohistochemistry (IHC) and RNA hybridization experiments suggest that although both isoforms are expressed in benign human prostate tissue, PPARγ1 predominates in PC tissue. Our results from PC cell line experiments suggest that PPARγ1 contributes to the proliferation of some PC cells and that PPARγ2 represses PC cell growth. Our findings also suggest that PPARγ1 increases the growth and possibly the transformation of otherwise benign prostate epithelial cells. These results help to establish different roles for PPARγ isoforms in prostate cells, and support the hypothesis that PPARγ1 acts as an oncogene and that PPARγ2 acts as a tumor suppressor in prostate cells.
由于前列腺癌（PC）的发病率不断上升且相关治疗费用高昂，迫切需要开发新的前列腺癌治疗和化学预防策略。尽管雄激素受体（AR）信号传导在前列腺癌的发生和发展中起着重要作用，但其他分子途径也有影响。过氧化物酶体增殖物激活受体γ（PPARγ）最近被认为是前列腺癌中的一种致癌基因，它可能影响癌症的发生和转移进程。PPARγ有两种亚型，PPARγ2在氨基末端额外有30个氨基酸。在此，我们研究了这两种亚型在良性和癌性前列腺上皮细胞中的差异表达和功能。我们的免疫组织化学（IHC）和RNA杂交实验结果表明，虽然两种亚型都在良性人前列腺组织中表达，但PPARγ1在前列腺癌组织中占主导地位。我们在前列腺癌细胞系实验中的结果表明，PPARγ1促进某些前列腺癌细胞的增殖，而PPARγ2抑制前列腺癌细胞的生长。我们的研究结果还表明，PPARγ1增加了原本良性的前列腺上皮细胞的生长并可能促进其转化。这些结果有助于确定PPARγ亚型在前列腺细胞中的不同作用，并支持PPARγ1在前列腺细胞中作为致癌基因而PPARγ2作为肿瘤抑制基因的假说。
