Transcription repressor Slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma
Transcription repressor Slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma
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DOI：
10.1158/1078-0432.ccr-05-0687
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发表时间：
2005-11-15
影响因子：
11.5
通讯作者：
Yang, PC
中科院分区：
文献类型：
--
作者：
Shih, JY;Tsai, MF;Yang, PC
目的：在先前的全基因组基因表达谱分析中，使用侵袭癌细胞系模型，我们已经确定Slug在高度侵袭性癌细胞中选择性过表达。本研究旨在探讨Slug在肺腺癌中的临床意义及其在癌细胞侵袭和转移过程中的作用。实验设计：采用实时荧光定量RT-PCR方法检测54例肺腺癌手术切除标本中Slug mRNA的表达及其与生存期的关系。结果：肺癌组织中Slug mRNA的高表达与术后复发（P = 0.03）和患者生存期缩短（P < 0.001）显著相关。Slug的过表达增强了异种移植肿瘤的生长，并在血管生成测定中增加了微血管计数。Slug的诱导型和组成型过表达均抑制了E-cadherin的表达，增强了体外侵袭能力。酶谱显示Slug过表达细胞中基质金属蛋白酶-2活性增加。ELISA、RT-PCR和免疫组化检测证实Slug过表达细胞和异种移植瘤中基质金属蛋白酶-2蛋白和mRNA表达增加。Slug是一个新的肺腺癌侵袭促进基因。
Purpose: In a previous genome-wide gene expression profiling analysis using an invasion cancer cell lines model, we have identified Slug as selectively overexpressed in the highly invasive cancer cells. Here, we investigated the clinical significance of Slug in lung adenocarcinoma and the role of Slug in the process of cancer cell invasion and metastasis.Experimental Design: Real-time quantitative reverse transcription-PCR was used to investigate Slug mRNA in surgically resected lung adenocarcinoma of 54 patients and its correlation with survival. We overexpressed Slug in a lung adenocarcinoma cell line with very low Slug levels and investigated the in vitro and in vivo effects of Slug expression.Results: High expression of Slug mRNA in lung cancer tissue was significantly associated with postoperative relapse (P = 0.03) and shorter patient survival (P < 0.001). The overexpression of Slug enhanced xenograft tumor growth and increased microvessel counts in angiogenesis assay. Both inducible and constitutive overexpression of Slug suppressed the expression of E-cadherin and increased the in vitro invasive ability. Zymography revealed increased matrix metalloproteinase-2 activity in Slug overexpressed cells. ELISA, reverse transcription-PCR, and immunohistochemistry confirmed the increase of matrix metalloproteinase-2 proteins and mRNA in Slug overexpressed cells and xenograft tumors.Conclusions: Slug expression can predict the clinical outcome of lung adenocarcinoma patients. Slug is a novel invasion-promoting gene in lung adenocarcinoma.