The mechanisms of pulmonary carciniogenesis in idiopathic pulmonary fibrosis

特发性肺纤维化的肺癌发生机制

• 批准号: 14570570
• 负责人: KUDOH Shoji
• 金额: $ 2.24万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570570/
• 关键词: Idiopathic pulmonary fibrosis; Carcinogenesis; cDNA array; Smad4; Transcriptional disorder; cDNA array; 肺癌; 発がん; 遺伝子異常; 遺伝子発現異常

Patients with Idiopathic pulmonary fibrosis (IPF) have an increased risk of developing lung cancer. To identify the key molecules involved in malignant transformation in IPF, we analyzed the expression profiles of lung tumor and paired lung tissue from patients with lung cancer and IPF (lung cancer/IPF) by cDNA array. Reduced expression of the Smad4 gene was frequently identified in tumor samples from lung cancers/IPF patients in real-time RT-PCR. In addition, mutational analysis of TGF-β type II receptor and Smad4 genes and analysis of the methylation status of the Smad4 promoter were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and methylation specific PCR (MSP) with subsequent sequencing analysis in this study. No mutation was detected in the eight tumor samples, but alterations of the Smad4 gene transcription were identified. Our findings indicated that Smad4 inactivation may play an important role in pulmonary carcinogensis or progression of lung cancer in IPF patients in which TGF-β is overexpressed, and that the alteration of Smad4 transcription may be one mechanism. These findings could be used to improve treatment of lung cancer patients with IPF.

特发性肺纤维化（IPF）患者患肺癌的风险增加。为了确定IPF中恶性转化涉及的关键分子，我们通过cDNA阵列分析了肺癌和IPF患者（肺癌/IPF）的肺肿瘤和配对肺组织的表达谱。在实时RT-PCR中，经常在肺癌/IPF患者的肿瘤样品中鉴定SMAD4基因的表达降低。此外，通过聚合酶链链反应链多态性（PCR-SSCP）和甲基化特异性PCR（MSP）检查了TGF-βII型受体和SMAD4基因的突变分析以及SMAD4启动子的甲基化状态的分析。在八个肿瘤样品中未检测到突变，但发现了SMAD4基因转录的改变。我们的发现表明，SMAD4失活在肺癌中可能起重要作用，或者在TGF-β过表达的IPF患者中肺癌的进展，而SMAD4转录的改变可能是一种机制。这些发现可用于改善IPF肺癌患者的治疗。

项目成果

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