Carcinogenesis in chronic epithelial damage of the lung

患有慢性上皮损伤的患者患肺癌的风险增加。为了确定参与这些患者恶性转化的关键分子，我们使用cDNA阵列和实时定量逆转录-聚合酶链反应（RT-PCR）分析了这些患者肺肿瘤和肺组织的表达谱。使用实时RT-PCR，在IPF肺癌患者的肿瘤样本中鉴定了转化生长因子-β（TGF-β）下游基因的表达改变，其中TGF-β过表达。提示TGF-β信号通路的失活可能在慢性上皮损伤患者的肺癌发生、发展过程中起重要作用。此外，我们还利用cDNA阵列、2D-DIGE和Ab-array分析了TGF-β暴露后TGF-β敏感上皮细胞表达谱的变化。许多分子被鉴定，其表达水平在TGF-β暴露后增加或减少。其中一个是关于EMT的。需要进一步研究该分子与Smads的关系。这些发现可用于制定预防措施或治疗慢性上皮损伤的肺癌患者。

Patients with chronic epithelium damage have an increased risk of developing lung cancer. To identify key molecules involved in malignant transformation in these patients, we analyzed the expression profiles of lung tumor and lung tissue from these patients using cDNA arrays and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Altered expressions of the genes downstream of transforming growth factor-β (TGF-β) were identified in tumor samples from lung cancer patients with IPF, in which TGF-β is overexpressed, using real-time RT-PCR. Our findings indicate that the inactivation of TGF-β signaling pathway may play an important role in pulmonary carcinogensis or progression of lung cancer in the patients with chronic epithelium damage. In addition, we analyzed the change of the expression profiles after TGF-β exposure in TGF-β-sensitive epithelial cells using cDNA array, 2D-DIGE, and Ab-array. Many molecules were identified, expression levels of which were increased or decreased after TGF-β exposure. One of those is concerned with EMT. Further study of the relationship of this molecule and Smads is required. These findings could be used to develop preventive measures or treatment of lung cancer patients with chronic epithelium damage.