Fritz Stephen B, Terrell Jeffrey E, Conner Edward R, Kukowska-Latallo Jolanta F, Baker James R
Center of Biological Nanotechnology, Division of Allergy and Clinical Immunology, The University of Michigan Medical Center, Ann Arbor, MI 48103-0648, USA.
J Allergy Clin Immunol. 2003 Dec;112(6):1057-63. doi: 10.1016/j.jaci.2003.09.042.
Nasal polyps are a common problem that is difficult to diagnose and treat, in part because the cause of nasal polyposis is unknown. Although information on the pathogenesis of polyposis is lacking, there are reports suggesting that a genetic predisposition underlies this disorder.
We sought to better understand the basis of nasal polyposis associated with allergic rhinitis. We hypothesize that the expression of unique genes is associated with the nasal polyposis phenotype.
We examined 12000 human genes transcribed in the nasal mucosa of patients with allergic rhinitis with and without nasal polyps. Biopsy specimens of the mucosa of patients with and without polyps were obtained after the patients refrained from the use of topical or systemic steroid therapy for 2 weeks.
Thirty-four genes were differentially expressed between the patient groups, including those for inflammatory molecules and putative growth factors. The greatest differential expression identified by the array analysis was for a group of genes associated with neoplasia, including mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared with control patients with rhinitis alone. Quantitative RT-PCR confirmed this differential expression and documented that the number of mammaglobin mRNA copies is actually 64-fold greater in tissues of patients with polyps versus control patients. The specificity of mammaglobin protein expression was evaluated by means of immunohistochemistry, which showed specific staining in nasal polyp mucosal goblet cells only in patients with polyps.
These data suggest that nasal polyposis involves deregulated cell growth, using gene activation in some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown function associated with breast neoplasia, might be related to polyp growth.
鼻息肉是一个常见问题,诊断和治疗都很困难,部分原因是鼻息肉病的病因不明。尽管缺乏关于息肉病发病机制的信息,但有报告表明这种疾病存在遗传易感性。
我们试图更好地了解与变应性鼻炎相关的鼻息肉病的基础。我们假设独特基因的表达与鼻息肉病表型相关。
我们检测了变应性鼻炎伴或不伴鼻息肉患者鼻黏膜中12000个人类基因的转录情况。在患者停用局部或全身类固醇治疗2周后,获取有或无息肉患者的黏膜活检标本。
两组患者之间有34个基因存在差异表达,包括炎症分子和假定生长因子的基因。阵列分析确定的最大差异表达是一组与肿瘤形成相关的基因,包括乳腺珠蛋白,与单纯鼻炎对照患者相比,息肉患者中该基因的转录水平高12倍。定量逆转录聚合酶链反应证实了这种差异表达,并记录到息肉患者组织中乳腺珠蛋白信使核糖核酸拷贝数实际上比对照患者高64倍。通过免疫组织化学评估乳腺珠蛋白蛋白表达的特异性,结果显示仅在息肉患者的鼻息肉黏膜杯状细胞中有特异性染色。
这些数据表明鼻息肉病涉及细胞生长失控,在某些方面利用基因激活,类似于肿瘤。此外,乳腺珠蛋白是一种与乳腺肿瘤相关但功能未知的基因,可能与息肉生长有关。