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癌症标志物中性粒细胞明胶酶相关脂质运载蛋白在人类子宫内膜增生中高度表达。

The cancer marker neutrophil gelatinase-associated lipocalin is highly expressed in human endometrial hyperplasia.

机构信息

Institute of Biochemical Science, College of Life Science, National Taiwan University, Taipei 10617, Taiwan.

出版信息

Mol Biol Rep. 2012 Feb;39(2):1029-36. doi: 10.1007/s11033-011-0828-9. Epub 2011 May 15.

DOI:10.1007/s11033-011-0828-9
PMID:21573795
Abstract

Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, β-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, β-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and β-catenin mRNA expression (r = -0.42 and r = -0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma.

摘要

最近,子宫内膜增生被认为比子宫腺肌病更容易发展为子宫内膜癌,风险更高。Lcn-2 基因编码中性粒细胞明胶酶相关脂质运载蛋白(NGAL),它促进细胞增殖,并在某些癌症中作为癌症标志物。在我们目前的研究中,我们调查了 NGAL 的表达与致病细胞因子以及与癌症相关的基因(包括环氧化酶-2(COX-2)、E-钙粘蛋白、β-连环蛋白和波形蛋白)在子宫内膜疾病患者中的关系。通过 Western blot、免疫组织化学和逆转录聚合酶链反应(RT-PCR)在增生和腺肌病活检样本中检测 NGAL 的表达。免疫组织化学显示 NGAL 发生在增生活检样本的腺上皮细胞中,但不在基质细胞中。子宫内膜增生中 NGAL 蛋白和 mRNA 的表达明显高于子宫内膜腺肌病。尽管我们的数据显示子宫内膜增生和子宫内膜腺肌病患者之间的致病细胞因子没有差异,但我们观察到子宫内膜增生患者中 COX-2、β-连环蛋白、波形蛋白和 E-钙粘蛋白的高表达水平。NGAL mRNA 表达与 COX-2 和 E-钙粘蛋白 mRNA 表达呈正相关(r = 0.41 和 r = 0.57),但与波形蛋白和 β-连环蛋白 mRNA 表达呈负相关(r = -0.42 和 r = -0.61)。我们的数据表明,NGAL 在子宫内膜增生患者中上调,以防止从增生向癌的转变。

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