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过氧化物酶体增殖物激活受体γ在前列腺腺癌中的表达

Expression of Peroxisome Proliferator Activated Receptor gamma in Prostatic Adenocarcinoma.

作者信息

Park Hyung Kyu, Kim HyunKyung, Kim Hyeong-Gon, Cho Young Mee, Jung Woon Yong, Han Hye Seung, Hwang Tae Sook, Kwon Ghee Young, Lim So Dug

机构信息

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

出版信息

J Korean Med Sci. 2015 May;30(5):533-41. doi: 10.3346/jkms.2015.30.5.533. Epub 2015 Apr 15.

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-γ ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-γ expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-γ antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-γ and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-γ except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-γ was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-γ mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-γ mRNA expression between low (≤7) and high (>7) Gleason score groups. There was no association of PPAR-γ mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-γ. Further studies are needed to assess the functional role of PPAR-γ and to validate its therapeutic implication in prostate cancer.

摘要

过氧化物酶体增殖物激活受体γ(PPAR-γ)是一种配体激活的转录因子,已被作为癌症治疗以及代谢紊乱的靶点进行研究。最近的研究表明,PPAR-γ配体由于具有抗增殖和促分化作用,在前列腺癌中具有抗肿瘤作用。本研究的目的是通过免疫组织化学和定量实时聚合酶链反应(PCR)验证PPAR-γ在恶性和良性前列腺组织中的表达。总共730例前列腺腺癌(PCA),包括63例根治性前列腺切除术标本的完整切片和含有667例PCA的组织芯片,用两种PPAR-γ抗体进行免疫染色。选择25例良性前列腺组织和PCA通过定量实时PCR研究mRNA表达。10.7%的PCA(78/730)显示PPAR-γ的细胞质免疫反应性,PCA中未观察到核免疫反应性。除了一些腺体中可变的弱细胞质染色外,大多数良性前列腺腺体显示PPAR-γ的阴性免疫反应性。在一些中央区和精阜黏膜上皮中观察到PPAR-γ的核免疫反应性。与良性组织相比,PCA中组成型PPAR-γ mRNA水平显著降低。低(≤7)和高(>7)Gleason评分组之间PPAR-γ mRNA表达没有差异。PPAR-γ mRNA水平或细胞质免疫染色与Gleason分级或病理分期无关。我们的研究支持了PPAR-γ核外定位和非基因组作用的证据。需要进一步研究来评估PPAR-γ的功能作用,并验证其在前列腺癌中的治疗意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3068/4414635/96dde283fc1b/jkms-30-533-g001.jpg

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