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Investigation of correlation between pulmonary fibrosis and carcinogenesis : Analysis about expression of p53, CD44 and nitric oxide synthase(NOS).

肺纤维化与癌变相关性研究：p53、CD44、一氧化氮合酶（NOS）表达分析。

基本信息

批准号：
10670552
负责人：
MATSUMOTO Mitsuhiro
金额：
$ 2.05万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670552/
关键词：
Lung cancer p53 CD44 Nitric oxide synthase Idiopathic interstitial pneumonia 特発生間質性肺炎繊維化 NOS

项目摘要

We examined expressions of tumor suppressor gene(p53), adhesion molecules(CD44 isoforms) and carcinogenic products(nitric oxide synthase : NOS) to investigate about correlation between pulomonary firosis and carcinogenesis.(1) Status of tumor suppressor gene p53 expression in lung cancer tissue, fibrotic tissue and non-tumorous tissue : We used an system of yeast p53 functional assay to examine an function of p53. We difined that p53 mutation occurred 63% of examined samples drived from primary lung cancer tissue(Int J Oncol., 12 ; 525-533, 1998). On the other hand, we could not comfirm that p53 mutation significantly occurred examined samples drived from pulmonary fibrosis tissue and also non-tumorous lung tissue.(2) Expression of adhesion molecules CD44 isoforms in lung cancer tissue, fibrotic tissue and non-tumorous tissue : We suggested that we could diagnosed whether sample specimens were malignancy or not from changes of CD44 isoforms ratio(J Natl Cancer Inst., 90 ; 307-315, 1998 … More ). Furthermore, CD44 cleavage plays a critical role in an efficient cell-detachment from a hyaluronate substrate during the cell migration and consequently promotes CD44-mediated cancer cell migration.(Oncogene.18 ; 1435-46, 1999) and also the Rho family proteins play a role in regulation of CD44 distribution and cleavage(J B C., 274 ; 25525-34, 1999). We could not find out any differences in fibrous lesions and also non-tumorous lesion about expressions of CD44 isoforms pattern.(3) Correlation between expressions of nitric oxide synthase(NOS) and p53 mutations in lung tissues : NO(nitric oxide) induces mutation in the p53 tumor suppressor gene ; we therefore analyzed the relationship between NO synthase(NOS) activity and p53 gene status in early-stage lung adenocarcinoma. NO has potential mutagenic and carcinogenic activity, and may play important roles in human lung adenocarcinoma(Jpn J Cancer Res., 89 ; 696-702, 1998). However, levels of NOS expression were unstable and we couldn't confirm high expression of bNOS in fibrotic lesions. We suggested that expressions of p53 mutation, CD44 isoforms and NOS were heterogeneous different from cancerous lesions. Less

我们检测肿瘤抑制基因（p53）、黏附分子（CD44亚型）和致癌产物（一氧化氮合酶：NOS）的表达，探讨肺纤维化与癌变的关系。(1)肿瘤抑制基因p53在肺癌组织、纤维化组织和非肿瘤组织中的表达状况：我们采用酵母p53功能检测系统检测p53的功能。我们确定p53突变发生在63%的来自原发性肺癌组织的检测样本中（Int J Oncol）。， 12；525 - 533, 1998)。另一方面，我们无法证实p53突变是否显著发生在来自肺纤维化组织和非肿瘤肺组织的检测样本中。(2)黏附分子CD44亚型在肺癌组织、纤维化组织和非肿瘤组织中的表达：我们建议可以通过CD44亚型比值的变化来诊断样本是否为恶性肿瘤（J Natl cancer institute, 90; 307-315, 1998…More）。此外，在细胞迁移过程中，CD44切割在细胞与透明质酸底物的有效分离中起着关键作用，从而促进CD44介导的癌细胞迁移。18;Rho家族蛋白在CD44分布和切割中的调控作用（J B C., 274; 25525- 34,1999）。我们没有发现在纤维病变和非肿瘤病变中CD44亚型的表达有任何差异。(3)肺组织一氧化氮合酶（NOS）表达与p53突变的相关性：NO（一氧化氮）诱导p53肿瘤抑制基因突变；因此，我们分析了NO合成酶（NOS）活性与早期肺腺癌中p53基因状态的关系。NO具有潜在的致突变和致癌活性，可能在人肺腺癌中发挥重要作用（Jpn J Cancer Res., 89; 696-702, 1998）。然而，NOS的表达水平不稳定，我们无法证实bNOS在纤维化病变中的高表达。我们认为p53突变、CD44亚型和NOS的表达在癌变灶中存在异质性。少