【作者】 杨慧；

【导师】 赵松；

【作者基本信息】 河北医科大学 ， 病理学与病理生理学， 2015， 硕士

【摘要】 目的:Notch信号传导系统在进化中是高度保守的,它在很多物种中都会存在,这种信号通路由受体、配体以及CSL(一类DNA结合蛋白)三部分构成。Notch受体本身是一个跨膜蛋白质,它分别由胞外区、跨膜区和胞内区构成。Notch受体的激活需要通过“三步裂解法”,其中在S3位点Notch受体分子在此区被水解成Notch蛋白的活化形式,即Notch胞内区(Notch-IC)。核定位序列可以作为胞内区的载体,通过CSL途径将胞内区介导入细胞核内,引起Notch的相关目标基因转录传递相关的生物信息。Hesr-1在内皮细胞血管形成中是发挥重要作用的一种转录抑制子,它也是HEY基因家族的成员之一,Hesr-1同时也是Notch信号通路的靶基因。然而Notch信号通路在肿瘤发生发展中又具有重要的意义,如Notch-1信号异常会导致乳腺癌发生,但是Notch-1和Hesr-1在乳腺癌的形成和发展中之间是否存在着相互关系的研究至今还未见报道。因此,本课题将研究Notch-1、Hesr-1在乳腺癌组织中的表达及其与乳腺癌临床病理特征的关系。方法:1研究对象:100例乳腺癌病例均来自邢台市人民医院2012年1月~2014年1月病理科存档石蜡包埋标本,从中随机抽取30例对应癌旁正常乳腺组织(距离癌组织2cm内的正常乳腺组织)石蜡标本作为对照组。2研究方法:组织切除后经10%中性甲醛固定后石蜡包埋备用。应用免疫组织化学技术检测100例乳腺癌组织及30例癌旁正常乳腺组织中Notch-1和Hesr-1蛋白的表达情况。结果:100例乳腺癌组织及30例癌旁正常乳腺组织中Notch-1阳性表达率为79.0%(79/100)和33.3%(10/30),乳腺癌组织中的Notch-1阳性表达率明显高于正常乳腺组织(P<0.05)。乳腺癌中的Notch-1阳性表达率与年龄无明显相关性(P>0.05),而与腋窝淋巴结转移、临床TNM分期和病理分级具有相关性(P<0.05);Hesr-1阳性表达率分别为68.0%(68/100)和30.0%(9/30),乳腺癌组织中的Hesr-1阳性表达率明显高于正常乳腺组织(P<0.05)。乳腺癌中的Hesr-1阳性表达率与年龄无相关性(P>0.05),而与腋窝淋巴结转移、临床TNM分期和病理分级具有相关性(P<0.05)。Notch-1和Hesr-1的蛋白表达呈正相关(r=0.225,P<0.05)。结论:Notch-1和Hesr-1的蛋白在乳腺癌中均呈高表达,可能协同促进乳腺癌的发生和发展,且可能在乳腺癌的浸润、转移及预后中发挥了重要作用。更多还原

【Abstract】 Objective: Notch signaling system is highly conserved in evolution,it will exist in it in many species,this signal pathway is consists of receptors,ligands and CSL.Notch itself is a transmembrane receptor protein,it respectively by the extracellular region,transmembrane region and intracellular region.Notch receptor activation by "three-step cracking method",which in the S3 sites Notch receptor molecules in the region protein was hydrolyzed into Notch activation form, namely Notch intracellular area(Notch- IC). check and ratify a sequence can be used as the carrier of intracellular area,CSL will area inside the cell mediated by into the nucleus and cause a Notch related target gene transcription related biological information.Hesr- 1 is play an important role in vascular endothelial cells to form a transcription of inhibition, it is also one of HEY gene family members.Hesr- 1 is Notch signaling pathways of target genes,and Notch signaling pathways in cancer development has the vital significance,such as the abnormal Notch-1 signaling can lead to breast cancer.However,the relationship of Notch-1 and Hesr-1 in breast cancer formation and development has not been reported. Therefore,this topic to study, Notch- 1、Hesr-1 expression in breast cancer tissue and its relationship with clinical pathological characteristics of breast cancer.Methods: 1Samples collection follow up:100 breast cancer cases were from xingtai people’s hospital from January 2012 to January 2014 department archive specimens of paraffin embedding,randomly selected from 30 cases of the corresponding normal breast tissue adjacent to carcinoma(cancer tissue within 2 cm of normal breast tissue) specimens of paraffin wax as the control group.2Experimental methods: The samples were fixed by 10%formal-dehyde, embeded in paraffin after excision.immunohistochemistry to detect the expression of Notch-1 and Hesr-1 protein in 100 cases of breast cancer tissues and 30 cases of normal breast tissues.Result: For 100 breast cancer tissue samples and 30 adjacent normal breast tissue samples,the positive rate of Notch-1 were 79.0%(79/100) and 33.3%(10/30),the positive rates of Notch-1 breast cancer tissue samples were significantly higher than those of adjacent normal breast tissue samples(P<0.05).The positive expression of Notch-1 of breast cancer was not significantly relevant to age(P>0.05),but was relevant to axillary lymph node metastasis,clinical TNM stage and pathological classification(P<0.05).The positive rates of Hesr-1 were 68.0%(68/100)and 30.0%(9/30). The positive rates of Hesr-1 of breast cancer tissue samples were significantly higher than those of adjacent normal breast tissue samples(P<0.05).The positive expression of Hesr-1 in breast cancer was not relevant to age(P>0.05),but was relevant to axillary lymph node metastasis,clinical TNM stage and pathological classification(P<0.05).The protein expression of Notch-1 and Hesr-1 were positively related(r=0.225,P<0.05).Conclusion: The expressions of Notch-1 and Hesr-1 of breast cancer are high and may promote the occurrence and development of breast cancer and play an important role in the invasion,metastasis,and prognosis of breast cancer.更多还原