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

我们检测了抑癌基因(P53)、黏附分子(CD44亚型)和致癌产物(一氧化氮合酶(NOS))的表达，以探讨肺纤维化与癌变的关系。(1)抑癌基因P53在肺癌组织、纤维化组织和非肿瘤组织中的表达状况：我们用酵母P53功能检测系统检测了P53的功能。我们发现63%的检测样本发生了P53突变(Int J Oncol.，12；525-533,1998)。(2)肺癌组织、肺纤维化组织和非肿瘤组织中黏附分子CD44亚型的表达：我们认为可以根据CD44亚型比值的变化来判断标本的恶性程度(J Natl Cancer Inst.，90；307-315,1998…更多)。此外，CD44的裂解在细胞迁移过程中有效地从透明质酸底物上分离起关键作用，从而促进CD44介导的癌细胞迁移(癌基因18；1435-46,1999年)以及Rho家族蛋白在调节CD44的分布和裂解中发挥作用(J BC C.，274；25525-34,1999)。(3)肺组织中一氧化氮合酶(NOS)表达与P53突变的相关性：一氧化氮(NO)可诱导P53抑癌基因突变，因此我们分析了早期肺腺癌中一氧化氮合酶(NOS)活性与P53基因状态的关系。NO具有潜在的致突变和致癌活性，并可能在人类肺腺癌中发挥重要作用(Jpn J癌症研究，89；696-702,1998)。然而，一氧化氮合酶的表达水平并不稳定，我们不能证实bNOS在纤维化病变中的高表达。提示P53突变、CD44亚型和NOS在不同癌变组织中的表达具有异质性。较少

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