DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.
DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.
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DOI：
10.1186/1471-2407-14-965
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发表时间：
2014-12-16
期刊：
影响因子：
3.8
通讯作者：
Garcia-Foncillas J
中科院分区：
文献类型：
--
作者：
Martinez-Useros J;Rodriguez-Remirez M;Borrero-Palacios A;Moreno I;Cebrian A;Gomez del Pulgar T;del Puerto-Nevado L;Vega-Bravo R;Puime-Otin A;Perez N;Zazo S;Senin C;Fernandez-Aceñero MJ;Soengas MS;Rojo F;Garcia-Foncillas J
DEK 是一种参与异染色质和十字形结构稳定的转录因子。它在不同类型癌症的发生和进展中发挥着重要作用。本研究旨在分析DEK在转移性结直肠癌中的作用。首先通过 WB 对 9 种结直肠细胞系和正常粘膜中的基线 DEK 表达进行定量。对 DLD1 和 SW620 中的短暂 DEK 沉默进行 SiRNA 介导的 DEK 抑制，以剖析其在结直肠癌侵袭性中的作用。使用 SN38 进行 24 小时内的伊立替康反应测定，并通过流式细胞术定量细胞凋亡。使用从手术切除中取出并用 SN38 处理 24 小时的 3 个新鲜肿瘤组织进行离体测定。通过免疫组织化学法测定 67 份福尔马林固定石蜡包埋的肿瘤样本中的 DEK 表达，这些样本来自接受伊立替康为一线治疗的转移性结直肠癌患者。 DEK 癌基因在所有结直肠癌细胞系中过度表达。 DEK 对 DLD1 和 SW620 细胞系的敲低可减少细胞迁移并增加伊立替康诱导的细胞凋亡。此外，低 DEK 表达水平预测 KRAS 野生型转移性结直肠癌患者基于伊立替康的化疗反应。这些数据表明 DEK 过度表达是结直肠癌侵袭性表型出现的关键事件，并且其作为 KRAS 野生型状态患者伊立替康反应生物标志物的潜在作用。
DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer. Baseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment. The DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type. These data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.
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