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

本研究通过检测肺癌组织中抑癌基因（p53）、粘附分子（CD 44亚型）和致癌产物（一氧化氮合酶（NOS））的表达，探讨肺癌与肺癌发生的关系。(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：我们使用酵母p53功能分析系统来检测p53的功能。我们确定p53突变发生在原发性肺癌组织中63%的受检样本中（Int J Oncol.，12 ; 525-533，1998）。另一方面，我们不能证实p53突变在肺纤维化组织和非肿瘤性肺组织中显著发生。(2)粘附分子CD 44亚型在肺癌组织、纤维化组织和非肿瘤组织中的表达：我们建议我们可以从CD 44亚型比率的变化诊断样本标本是否为恶性（J Natl Cancer Inst.，90 ; 307-315，1998年 ...更多信息 ).此外，CD 44裂解在细胞迁移期间有效细胞脱离透明质酸盐基质中起关键作用，因此促进CD 44介导的癌细胞迁移。（Oncogene.18 ; 1435-46，1999）以及Rho家族蛋白在调节CD 44分布和切割中起作用（J B C.，274 ; 25525-34，1999）。在纤维性病变和非肿瘤性病变中CD 44亚型的表达无明显差异。(3)肺组织中一氧化氮合酶（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。NO具有潜在的致突变和致癌活性，并且可能在人肺腺癌中起重要作用（Jpn J Cancer Res.，89 ; 696-702，1998）。然而，NOS的表达水平是不稳定的，我们不能证实bNOS在纤维化病变中的高表达。提示p53突变、CD 44亚型和NOS的表达与癌组织不同。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