ANALYSIS OF CHROMOSOMAL AND CANCER RELATED GENE ABNORMALITIES IN ATYPICAL EPITHELIUM IN THE RESPIRATORY SYSTEM

呼吸系统非典型上皮染色体和癌症相关基因异常分析

基本信息

批准号：
12670562
负责人：
NAKANISHI Yoichi
金额：
$ 0.51万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670562/
关键词：
ATYPIACAL EPITHELIUM GENE CHROMOSOME p53 LOH LUNG CANCER FHIT PRECANCEROUS LESION 異型上皮発癌 K-ras

项目摘要

Molecular biological analysis was performed using specimens derived from transbronchial biopsy (TBB) to confirm the following hypotheses;(1)Chromosomal and cancer related gene abnormalities occur in concordance with the degree of epithelial atypia in respiratory system such as bronchial and alveolar epithelium.(2)Epithelial atypia found in cancer patients is molecularbiologically different from that found in non-cancerous patients.TBB specimens were classified according to the degree of their cellular atypia into hyperplasia, metaplasia, and dysplasia. After isolation of atypical epithelia by microdissection method, DNA was extracted and analyzed. Loss of heterozygosity (LOH) in 3pl4.2 (FHIT), 3p21.3, 8p22, 9p22, 18q21.1 were evaluated. In addition, the expression of p53, PCNA and p21 was compared to the degree of apoptosis.LOH in 3p21.3 and 9p22 occurred in early stage of lung carcinogenesis and was significantly related to the degree of cellular atypia. LOH in 8p22 and 18q21.1 occurr … More ed in middle or late stage of lung carcinogenesis. LOH of 3pl4.2 (FHIT) was not related to the degree of cellular atypia, and found selectively in smokers. Interestingly, these LOH were frequently found in patients with lung cancer and with idiopathic pulmonary fibrosis (IPF), and infrequently found in patients with other benign lung diseases. The results suggest that the frequent occurrence of lung cancer in patients with IPF, at least in part, reflects the frequent occurrence of chromosomal abnormalities in atypical epithelium in IPF.Previously, we reported that epithelial atypical epithelium frequently express wild-type p53 protein (Wakamatsu et al, Am J Respir Cell Mol Biol, 1999). In the present study, we found that p53 expression significantly related to PNCA expression, but not to p21 expression or to apoptosis. From the in vitro experiments, we showed that smoking related chemical carcinogens such as benzo[a]pyrene induce the expression of p53 protein, but that ubiquitinate p21 protein immediately after its expression resulting in the blockade of cell cycle arrest. This result elucidate the reason why the expression of (wild-type) p53 is not related to the expression of p21 in atypical epithelium in the respiratory system.These results indicated that various chromosomal abnormalities are found in atypical epithelium in the respiratory system, and that the frequency of chromosomal abnormalities are more common in cellular atypia found in patients with lung cancer and IPF than those with other benign diseases. Less

使用经过经过支气管活检（TBB）得出的物种进行了分子生物学分析，以确认以下假设；（1）（1）染色体和癌症与癌症和癌症相关的基因异常与呼吸系统中的上皮性异型的程度一致，例如呼吸系统中的呼吸系统和e骨上皮菌（2）上皮菌（2）Intipia Inspity iniptia iniptia iniptia in timelial。非癌症患者。TBB物种根据其细胞异常程度分类为增生，化生和发育不良。通过微分解方法分离非典型上皮细胞后，提取并分析了DNA。评估了3PL4.2（FHIT），3P21.3、8P22、9P22、18Q221.1中杂合性损失（LOH）。此外，将p53，pCNA和p21的表达与凋亡的程度进行了比较。3p21.3和9p22中的LOH发生在LOH的早期8p22和18q21.1发生……在LOH的中间或晚期发生的ED发生在LOH的中期或晚期3PL4.2（FHIT）（FHIT）的中间或晚期与CellarulAcel Atpia Atypia Anpipia Anipe and Invefiale Inspia and Inspia and Inspia无关。有趣的是，这些LOH经常在肺癌患者和特发性肺纤维化（IPF）中发现，并且在其他良性肺部疾病的患者中很少发现。结果表明，IPF患者的肺癌经常发生，至少部分反映了IPF中非典型上皮层染色体异常的发生。在本研究中，我们发现p53表达显着相关。 pNCA表达，但不能表达p21或凋亡。从体外实验中，我们表明与吸烟相关的化学致癌物（例如苯并[A] pyrene）诱导p53蛋白的表达，但泛素酸p21蛋白在表达后立即导致细胞周期停滞的阻断。该结果阐明了（野生型）p53的表达与呼吸系统中非典型上皮细胞中p21的表达无关。这些结果表明，在呼吸系统中，在呼吸系统中的非典型上皮中发现了各种染色体异常，以及其他常见的collnormal collumal consipia confiquia的频率，是在呼吸系统上的频率。良性疾病。较少的