中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《生命科学》 2007, 19(6): 592-
受体型酪氨酸激酶RON在人细支气管肺泡癌发病机理中的作用
王明海*,姚航平,周永庆
浙江大学医学院附属第一医院,肿瘤生物学和实验治疗实验室, 杭州 310003
摘 要:细支气管肺泡癌(bronchioloalveolar carcinoma, BAC)是一种以在肺泡和终末细支气管生长为主要特征的肺癌,占全部肺癌的5%-10%。近期BAC的发病率呈上升趋势。绵羊肺腺病是一种在病理形态上与人BAC极其类似的肺恶性肿瘤,病因是Jaagsiekte绵羊逆转录病毒。然而,人BAC的病因及发病机理至今不明。受体型酪氨酸激酶RON是原癌基因MET家族的一员,RON及其变异体在人BAC样品中呈高度的异常表达。 转基因小鼠的实验进一步证明,定向性的在肺泡二型上皮细胞中表达RON,能诱发具有人BAC特征的小鼠肺肿瘤,RON致癌的基础是其传导的异常信息途径。采用特异性siRNA和单克隆抗体干扰RON的表达,能抑制RON介导的BAC的生长。因此,RON的异常表达是特异性药物作用的靶点,阐明原癌基因RON在BAC发病机理中的作用具有重要的临床意义。
关键词:细支气管肺泡癌;受体型酪氨酸激酶;发病机理;单克隆抗体;实验性治疗
中图分类号:R734.2;Q55  文献标识码:A
 
Receptor tyrosine kinase RON in the pathogenic progressionof human bronchioloalveolar carcinoma
WANG Minghai*, YAO Hangping, ZHOU Yongqing
(Laboratory of Cancer Biology and Therapeutics, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China)

Abstract: Bronchioloalveolar carcinoma (BAC), accounting for 5%-10% of total lung cancers with increased incidence in recent years, is characterized by growth of tumors in alveolar sacks and terminal bronchioles in the lung. Pathologically, BAC resembles to sheep pulmonary adenomatosis, a malignant disease caused by Jaagsiekte sheep retrovirus. Currently, the cause and the underlying mechanism of human BAC are unknown. The RON receptor tyrosine kinase belongs to the MET proto-oncogene family. RON and its variants are aberrantly expressed at high levels in the majority of BAC samples. Studies from transgenic mice showed that targeted expression of RON in type II lung cells results in tumor formation with features of human BAC. The pathogenic basis is RON-transduced tumorigenic signals. Blocking RON expression by specific siRNA or monoclonal antibodies inhibits RON-mediated tumor growth. Thus, altered RON expression is a potential drug target. Determining the roles of RON in the development of BAC should have important clinical implications.  
Key words: bronchioloalveolar carcinoma; receptor tyrosine kinase; pathogenic mechanism; monoclonal antibody; therapeutics

 
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