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原发肿瘤和胸水中的乳腺癌细胞具有不同的基因阵列谱。

Breast carcinoma cells in primary tumors and effusions have different gene array profiles.

机构信息

Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.

出版信息

J Oncol. 2010;2010:969084. doi: 10.1155/2010/969084. Epub 2009 Aug 11.

Abstract

The detection of breast carcinoma cells in effusions is associated with rapidly fatal outcome, but these cells are poorly characterized at the molecular level. This study compared the gene array signatures of breast carcinoma cells in primary carcinomas and effusions. The genetic signature of 10 primary tumors and 10 effusions was analyzed using the Array-Ready Oligo set for the Human Genome platform. Results for selected genes were validated using PCR, Western blotting, and immunohistochemistry. Array analysis identified 255 significantly downregulated and 96 upregulated genes in the effusion samples. The majority of differentially expressed genes were part of pathways involved in focal adhesion, extracellular matrix-cell interaction, and the regulation of the actin cytoskeleton. Genes that were upregulated in effusions included KRT8, BCAR1, CLDN4, VIL2, while DCN, CLDN19, ITGA7, and ITGA5 were downregulated at this anatomic site. PCR, Western blotting, and immunohistochemistry confirmed the array findings for BCAR1, CLDN4, VIL2, and DCN. Our data show that breast carcinoma cells in primary carcinomas and effusions have different gene expression signatures, and differentially express a large number of molecules related to adhesion, motility, and metastasis. These differences may have a critical role in designing therapy and in prognostication for patients with metastatic disease localized to the serosal cavities.

摘要

在胸腔积液中检测到乳腺癌细胞与迅速致命的结局相关,但这些细胞在分子水平上的特征描述较差。本研究比较了原发性癌和胸腔积液中乳腺癌细胞的基因表达谱。使用 Human Genome 平台的 Array-Ready Oligo 集分析了 10 个原发性肿瘤和 10 个胸腔积液样本的基因谱。使用 PCR、Western blotting 和免疫组织化学验证了选定基因的结果。基因芯片分析鉴定出胸腔积液样本中有 255 个明显下调和 96 个上调的基因。差异表达基因的大多数是参与局灶黏附、细胞外基质-细胞相互作用和肌动蛋白细胞骨架调节的途径的一部分。在胸腔积液中上调的基因包括 KRT8、BCAR1、CLDN4、VIL2,而 DCN、CLDN19、ITGA7 和 ITGA5 在该解剖部位下调。PCR、Western blotting 和免疫组织化学证实了 BCAR1、CLDN4、VIL2 和 DCN 的基因芯片结果。我们的数据表明,原发性癌和胸腔积液中的乳腺癌细胞具有不同的基因表达谱,并且差异表达大量与黏附、运动和转移相关的分子。这些差异可能在设计治疗方案和预测有浆膜腔局部转移的患者预后方面具有重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dde9/2725284/db85ea666c5c/JO2010-969084.001.jpg

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