Gene expression profiling identifies matriptase overexpression in malignant mesothelioma
Gene expression profiling identifies matriptase overexpression in malignant mesothelioma
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DOI：
10.1378/chest.125.5.1843
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发表时间：
2004-05-01
期刊：
影响因子：
9.6
通讯作者：
Kratzke, RA
中科院分区：
文献类型：
--
作者：
Hoang, CD;D'Cunha, J;Kratzke, RA
研究目的：我们研究了恶性胸膜间皮瘤 (MPM) 标本的基因表达谱，以确定可能参与人类胸膜细胞致癌转化的新基因。设计：使用分层聚类对 10 个 MPM 细胞系和 4 个 MPM 原发性肿瘤标本进行互补 DNA (cDNA) 微阵列转录谱研究。为了确认微阵列数据，我们使用了实时聚合酶链式反应和免疫印迹。结果：聚类分析区分上皮 (E)、肉瘤样和双相 MPM 变异。表达谱鉴定了 MPM 中常见的过表达或表达不足的基因。值得注意的是，matriptase 信使 RNA 在 E MPM 中过表达 826 倍，随后通过免疫印迹分析证实了蛋白质表达。这种最近鉴定的胰蛋白酶样丝氨酸蛋白酶与 E 衍生癌症的肿瘤侵袭和转移有关，但迄今为止尚未在 MPM 中得到描述。我们还鉴定了其他新基因，例如胰岛素样生长因子结合蛋白 5 和类似于蛋白脂质 MAL2 的 cDNA 克隆。 结论：因此，进一步大规模的 MPM 分析可以通过鉴定参与恶性转化的新基因来阐明以前未识别的分子机制。我们的研究现已发现matriptase是这些间皮瘤相关基因之一，具有潜在的致病和治疗意义。
Study objective: We investigated the gene expression profiles of malignant pleural mesothelioma (MPM) specimens to identify novel genes that are potentially involved in the oncogenic transformation of human pleural cells.Design: Complementary DNA (cDNA) microarray transcriptional profiling studies of 10 MPM cell lines and 4 MPM primary tumor specimens were performed using hierarchic clustering. To confirm microarray data, we used real-time polymerase chain reaction and immunoblotting.Results: Cluster analysis differentiated among epithelial (E), sarcomatoid, and biphasic MPM variants. Expression profiling identified common overexpressed or underexpressed genes in MPM. Notably, matriptase messenger RNA was found to be overexpressed by 826-fold in E MPM, with protein expression subsequently confirmed by immunoblot analysis. This recently characterized trypsin-like serine protease has been implicated in tumor invasion and metastasis of E-derived cancers, but has not been described until now in MPM. We also identified other novel genes, such as insulin-like growth factor binding protein 5 and a cDNA clone similar to proteolipid MAL2.Conclusions: Thus, further large-scale profiling of MPM may elucidate previously unrecognized molecular mechanisms by identifying novel genes that are involved in malignant transformation. Our study has now found matriptase to be one of these mesothelioma-associated genes, with potential pathogenic and therapeutic significance.