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Study of cell proliferation and oncogenesis in pulmonary fibrosis. Kyushu University Research Institute for Diseases of the Chest

肺纤维化细胞增殖和肿瘤发生的研究。

基本信息

批准号：
08670666
负责人：
HARA Nobuyuki
金额：
$ 1.41万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670666/
关键词：
IIP lung cancer p53 Fas PCNA apoptosis 癌抑制遺伝子p53 肺線維症 Fas・Fas Lシステム

项目摘要

It is reported that 7% to 30% of patients with idiopathic interstitial pneumonia (IIP) are associated with lung cancer. Inversely, 8% of patients with lung cancer are associated with IIP,and 35%of patients with lung cancer have pulmonary interstitial changes. These facts indicate that pulmonary fibrosis has an important role as a background of lung carcinogenesis. We haveinvestigated the mechanisms of cell proliferation and carcinogenesis for the lung tissue from 20 patients with lung cancer associated with pulmonary interstitial changes.In cancer tissue immunohistochemical expression of p53 was observed in 70% of the cases. while, in alveolar and bronchiolar epithelium of fibrosis area, it was observed in 45% of the cases. In fibrosis area, the staining intensity was lower, and the staining pattern was scattered. Positive ratio of PCNA was 90% in cancer area, and 60% in fibrosis area in which positive area was distributed unequally around bronchial epithelium. No expression of Fas was seen in cancer area. Positive ratio of TUNEL stain in fibrotic area was 50%. In the cases multiple area was anlyzed by step section for p53 expression, PCNA expression and TUNEL stain, co-expression of p53 and PCNA, and simultaneous DNA damage were foca11y observed.These results indicate that both cell proliferatioh and cell damage (or apoptosis) occur simultaneously in tissue exhibiting pulmonary fibrosis. Thus, it is suggested that DNA damage and repair are seen in the tissue with pulmonary flbrosis, leading to luhg carcinogenesis. In order to clarify whether p53 expression in pulmonary fibrosis represents p53. mutation as precancerous lesion or expression of wild type p53 to preserve DNA stability, p53 gene analysis ln these area are now ongoing.

据报道，7%至30%的特发性间质性肺炎（IIP）患者与肺癌相关。相反，8%的肺癌患者伴有IIP，35%的肺癌患者存在肺间质改变。这些事实表明肺纤维化作为肺癌发生的背景具有重要作用。我们对20例伴有肺间质改变的肺癌患者的肺组织进行了细胞增殖和癌变的机制研究，其中70%的病例在癌组织中观察到p53的免疫组化表达。而在肺泡和细支气管上皮的纤维化区域，有45%的病例出现这种现象。纤维化区域染色强度较低，染色图案分散。癌区PCNA阳性率为90%，纤维化区PCNA阳性率为60%，且阳性区域在支气管上皮周围分布不均匀。癌区未见Fas表达。纤维化区域TUNEL染色阳性率为50%。在对多个区域进行阶梯切片分析p53表达、PCNA表达和TUNEL染色、p53和PCNA共表达以及同时DNA损伤的情况下，重点观察到。这些结果表明，在表现出肺纤维化的组织中，细胞增殖和细胞损伤（或凋亡）同时发生。因此，表明肺纤维化组织中存在DNA损伤和修复，从而导致癌变。为了明确p53在肺纤维化中的表达是否代表p53。突变作为癌前病变或表达野生型 p53 以保持 DNA 稳定性，这些领域的 p53 基因分析目前正在进行中。