The expression and prognostic value of the guanine nucleotide exchange factors (GEFs) Trio, Vav1 and TIAM-1 in human breast cancer.
The expression and prognostic value of the guanine nucleotide exchange factors (GEFs) Trio, Vav1 and TIAM-1 in human breast cancer.
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DOI：
10.1186/1477-7800-5-23
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发表时间：
2008-10-16
期刊：
影响因子：
--
通讯作者：
Jiang, Wen G
中科院分区：
文献类型：
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作者：
Lane, Jane;Martin, Tracey A;Jiang, Wen G
背景技术背景：乳腺癌转移的发展是一个多步骤的过程，包括肿瘤细胞的细胞骨架结构和基因表达的变化，导致细胞粘附和运动性的变化。Rho GT3蛋白作为鸟嘌呤核苷酸调节的二元开关发挥作用，控制各种细胞过程，包括细胞运动和迁移、细胞粘附的变化以及肌动蛋白细胞骨架重组和基因表达/转录。调节Rho-GTPases的一组激活剂是鸟嘌呤核苷酸交换因子（GEF），本研究研究了三种这样的GEF，Trio，Vav 1和TIAM-1。本研究的目的是调查这些GEFs的表达，在人类乳腺癌和评估对临床outcome.METHODS的影响：新鲜，冷冻乳腺癌组织（n = 113）和正常背景组织（n = 30）标本进行定量PCR分析。采用RT-PCR和实时定量PCR分别分析Trio、Vav 1和TIAM-1的表达和表达水平。切片也用Trio和Tiam-1抗体进行免疫染色。结果：与正常背景乳腺组织相比，肿瘤组织显示出高水平的所有三种Rho激活剂Trio、Vav 1和TIAM-1，达到GEF Trio的显著水平（p = 0.013）。Trio水平在预后不良的患者中也显著增加（p = 0.04）。与存活的患者相比，死于乳腺癌的患者的肿瘤组织中TIAM-1水平显著更高（p = 0.04）。结论：Trio、Vav 1和TIAM-1在乳腺肿瘤中呈高表达，尤其是预后不良的乳腺肿瘤。这表明GEFs对Rho家族活性的异常调节可能对乳腺癌具有重要的预后价值。
BACKGROUND: Development of metastasis in breast cancer is a multi-step process comprising changes in cytoskeletal structure and gene expression of tumour cells leading to changes in cell adhesion and motility. The Rho GTPase proteins, which function as guanine nucleotide regulated binary switches, govern a variety of cellular processes including cell motility and migration, changes in cell adhesion as well as actin cytoskeletal reorganisation and gene expression/transcription. One group of activators which regulate the Rho-GTPases is the guanine nucleotide exchange factors (GEFs), and this study looked at three such GEFs, Trio, Vav1 and TIAM-1. The purpose of this study was to investigate the expression of these GEFs, in human breast cancer and assess the affect on clinical outcome.METHODS: Specimens of fresh, frozen breast tumour tissue (n = 113) and normal background tissue (n = 30) were processed for quantitative PCR analysis. The expression and levels of expression of Trio, Vav1 and TIAM-1 were analysed using RT-PCR and real-time Q-PCR respectively. Sections were also immunostained with Trio and Tiam-1 antibodies.RESULTS: Tumour tissue exhibited high levels of all three Rho activators Trio, Vav1 and TIAM-1 compared with normal background breast tissue, reaching a level of significance for the GEF Trio (p = 0.013). Trio levels also increased significantly in patients with a poor prognostic index (p = 0.04).Levels of TIAM-1 were significantly higher in tumour tissue from patients who died from breast cancer compared with those who survived (p = 0.04). No significant correlation was found between tumour grade and histology types.CONCLUSION: High expression levels of Trio, Vav1 and TIAM-1 were seen in breast tumours, especially in those with poor prognosis. This suggests that aberrant regulation of Rho family activities by GEFs may have an important prognostic value in breast cancer.