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骨桥蛋白表达与核因子-κB 活化及肾透明细胞癌细胞凋亡下调相关。

Osteopontin expression correlates with nuclear factor-κB activation and apoptosis downregulation in clear cell renal cell carcinoma.

机构信息

Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia.

出版信息

Pathol Res Pract. 2011 Feb 15;207(2):104-10. doi: 10.1016/j.prp.2010.11.004. Epub 2010 Dec 16.

DOI:10.1016/j.prp.2010.11.004
PMID:21167650
Abstract

Osteopontin (OPN) is a phosphoglycoprotein implicated in tumorigenesis and tumor cell metastasis. Apoptosis inhibition is one of the mechanisms that contribute to development and progression of cancer, and might be initiated by OPN interaction with tumor cells. The aim of this study was to analyze the relation between OPN and nuclear factor-kappa B (NF-κB) expression in clear cell renal cell carcinoma (CCRCC), as well as their relation to apoptotic activity of tumor cells. Expression of OPN protein and p65 NF-κB subunit was analyzed immunohistochemically in 87 CCRCC samples, and compared mutually and with apoptotic index. Expression of OPN mRNA was analyzed using quantitative real-time PCR and compared with OPN and NF-κB protein expression in 22 CCRCC samples. Statistical analysis showed an association of p65 NF-κB with OPN mRNA (p=0.015) and protein (p<0.001). Also, we found an inverse relationship of OPN with NF-κB protein expression and apoptotic activity of tumor cells (p=0.006 and p=0.022, respectively). Our results indicate that p65 NF-κB signaling pathway may be involved in OPN-mediated CCRCC progression, partly by protecting tumor cells from apoptosis. Therefore, both molecules can constitute potential targets for therapeutic intervention in CCRCC.

摘要

骨桥蛋白(OPN)是一种参与肿瘤发生和肿瘤细胞转移的磷酸糖蛋白。细胞凋亡抑制是癌症发展和进展的机制之一,可能是由 OPN 与肿瘤细胞相互作用引发的。本研究旨在分析透明细胞肾细胞癌(CCRCC)中 OPN 和核因子-κB(NF-κB)表达之间的关系,以及它们与肿瘤细胞凋亡活性的关系。在 87 例 CCRCC 样本中,通过免疫组织化学分析 OPN 蛋白和 p65 NF-κB 亚基的表达,并相互比较,与凋亡指数进行比较。使用定量实时 PCR 分析 OPN mRNA 的表达,并与 22 例 CCRCC 样本中的 OPN 和 NF-κB 蛋白表达进行比较。统计分析显示,p65 NF-κB 与 OPN mRNA(p=0.015)和蛋白(p<0.001)相关。此外,我们发现 OPN 与 NF-κB 蛋白表达和肿瘤细胞凋亡活性呈负相关(p=0.006 和 p=0.022)。我们的结果表明,p65 NF-κB 信号通路可能参与了 OPN 介导的 CCRCC 进展,部分是通过保护肿瘤细胞免受凋亡。因此,这两种分子都可以成为 CCRCC 治疗干预的潜在靶点。

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