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）患者发生肺癌的风险增加。为了确定参与IPF恶性转化的关键分子，我们通过cDNA阵列分析了肺癌和IPF（lung cancer/IPF）患者的肺肿瘤和配对肺组织的表达谱。在实时RT-PCR中，在肺癌/IPF患者的肿瘤样本中经常发现Smad 4基因表达降低。此外，采用聚合酶链反应-单链构象多态性分析（PCR-SSCP）和甲基化特异性PCR（MSP）检测TGF-β II型受体和Smad 4基因的突变，并对Smad 4启动子甲基化状态进行分析。在8个肿瘤样本中未检测到突变，但确定了Smad 4基因转录的改变。我们的研究结果表明，Smad 4失活可能在TGF-β过表达的IPF患者的肺癌发生或进展中起重要作用，Smad 4转录的改变可能是一种机制。这些发现可用于改善肺癌伴IPF患者的治疗。

项目成果

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