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分析人支气管和肺外周组织中整个细胞色素 P450 超家族的基因表达:非小细胞肺癌中的差异表达。

Profiling gene expression of whole cytochrome P450 superfamily in human bronchial and peripheral lung tissues: Differential expression in non-small cell lung cancers.

机构信息

Equipe d'accueil EA2679, Faculté de Médecine Pôle Recherche, Université Lille Nord de France, Place de Verdun, Lille, France.

出版信息

Biochimie. 2010 Mar;92(3):292-306. doi: 10.1016/j.biochi.2009.12.007. Epub 2009 Dec 23.

DOI:10.1016/j.biochi.2009.12.007
PMID:20034539
Abstract

Susceptibility to lung diseases, such as lung cancer and chronic obstructive pulmonary disease, is largely influenced by the metabolic capacity of lung tissues. This capacity is partly determined by the expression profile of the cytochromes P450 (CYPs), a superfamily of enzymes that have relevant catalytic properties toward exogenous and endogenous compounds. Using quantitative real-time RT-PCR, we conducted a comprehensive analysis of the expression profile of the 57 human CYP genes in non-tumoral (bronchial mucosa and pulmonary parenchyma) and tumoral lung tissues of 18 patients with non-small cell lung cancer. This study highlights (i) inter-individual variations in lung expression for some CYPs, (ii) different CYP expression patterns between bronchial mucosa and pulmonary parenchyma, that indicate distinctive susceptibility of these tissues toward the deleterious effects of inhaled chemical toxicants and carcinogens, (iii) high intertumoral variability, that could have major implications on lung tumor response to anti-cancer drugs.

摘要

肺部疾病(如肺癌和慢性阻塞性肺疾病)的易感性在很大程度上受肺部组织代谢能力的影响。这种能力部分取决于细胞色素 P450(CYP)的表达谱,CYP 是一组具有对外源和内源性化合物相关催化特性的酶。本研究采用定量实时 RT-PCR 方法,对 18 例非小细胞肺癌患者非肿瘤(支气管黏膜和肺实质)和肿瘤肺组织中 57 个人类 CYP 基因的表达谱进行了全面分析。本研究突出了以下几点:(i)某些 CYP 在肺组织中的个体间表达存在差异;(ii)支气管黏膜和肺实质之间 CYP 表达模式的不同,表明这些组织对吸入化学毒物和致癌物的有害影响具有不同的易感性;(iii)肿瘤间的高度变异性,这可能对肺癌肿瘤对抗癌药物的反应产生重大影响。

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