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

我们通过检测抑癌基因（p53）、粘附分子（CD44亚型）和致癌产物（一氧化氮合酶：NOS）的表达来探讨肺泡纤维化与癌变之间的相关性。（1）肺癌中抑癌基因p53的表达状况组织、纤维化组织和非肿瘤组织：我们使用酵母 p53 功能测定系统来检查 p53 的功能。 p53突变发生在来自原发性肺癌组织的检查样本中63%(Int J Oncol., 12; 525-533, 1998)。另一方面，我们无法证实p53突变在来自肺纤维化组织的检查样本中显着发生。 (2)粘附分子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 同工型比例的变化来诊断样本是否为恶性肿瘤（J Natl Cancer Inst., 90 ; 307-315, 1998 … More ）。此外，CD44 裂解在高效细胞中起着至关重要的作用。 -在细胞迁移过程中与透明质酸基质分离，从而促进 CD44 介导的癌细胞迁移。（Oncogene.18； 1435-46, 1999) 以及 Rho 家族蛋白在 CD44 分布和切割的调节中发挥作用 (J B C., 274; 25525-34, 1999) 我们无法发现纤维性病变和非病变中的任何差异。肿瘤病灶与CD44亚型表达模式的关系。 (3)一氧化氮表达的相关性肺组织中NO合酶（NOS）和p53突变：NO（一氧化氮）诱导p53抑癌基因突变；因此，我们分析了早期肺腺癌中NO合酶（NOS）活性与p53基因状态之间的关系。潜在的诱变和致癌活性，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 表达水平不稳定，我们无法证实纤维化病变中 bNOS 的高表达，我们认为 p53 突变、CD44 亚型和 NOS 的表达与癌性病变不同。