【作者】 葛亚东；

【导师】 聂刘旺；

【作者基本信息】 安徽师范大学 ， 动物学， 2005， 硕士

【摘要】 一、文献综述1、肿瘤是多病因参与并经历多阶段的发病和演进的过程而产生的,其本质是一种分子病,是某些基因异常改变的结果。结肠癌是较常见的恶性肿瘤,在结肠癌发生的病因学中,主要有3 类基因的突变,即癌基因(oncogene)、肿瘤抑制基因(suppressor genes)以及错配修复基因(mismatch repair gene,MMR)突变。本文就上述基因在结肠癌中的研究作一综述。2、SOX 基因是一类与SRY 基因紧密相关的编码转录因子的基因家族,其产物的共同特点是具有一个HMG 基序保守区,可与DNA 序列特异结合,参与多种发育过程的调控。在人类,SOX 基因的缺失或突变可导致许多先天性疾病。如人类SOX9 突变可引起CD 综合征和性反转,SOX10 突变与Waardenburg 综合征(WS)等。本文综述了近年来SOX 基因突变及异常表达与人类相关疾病发生关系的研究进展。二、研究报告1、本研究采用PCR—SSCP 技术,对13 例结肠癌及其癌旁组织进行了SOX4 基因突变分析,结果在13 例结肠癌组织中检测出5 例伴有SOX4 基因突变,而其相应癌旁组织中均未检出有突变。2、SOX 基因是以SRY 基因为基本成员的一类新的控制发育的基因家族,其编码产物为一类重要的转录调控因子。研究显示:SOX 基因家族中的SOX4基因可能通过影响其下游基因的转录调控,从而诱导结肠癌的发生。本研究中,我们克隆了5 例经PCR-SSCP 检测有突变结肠癌组织的SOX4 基因HMG-box区序列,测序后与正常人SOX4 的序列比较发现HMG-box 区均有突变,分别位于10541bp、10580 bp、10476 bp、10485 bp、10518 bp、10648 bp 和10666 bp处,而与之作对比的癌旁组织均无突变,提示SOX4 基因HMG-box 的突变可能导致了结肠癌的发生与发展。本文首次报道了结肠癌组织中SOX4 基因突变的情况,以期能从分子生物学水平上探讨结肠癌的发生机理,为预测结肠癌发生、患者临床预后以及结肠癌早期诊断提供的分子依据。更多还原

【Abstract】 PartⅠ: Reviews 1. Tumor`s development involves many kinds of factors and through several stages. The essence of the tumor is molecular diease. It is the result of the abnormal changes in genes. Colorectal cancer is a kind of usual malignant tumor. The origination of this tumor involves 3 kinds of gene mutations, namely, oncogene、suppressor gene and mismatch repair gene (MMR) . In this article , we reviewed the studies on oncogene、suppressor gene and mismatch repair gene in colorectal cancer. 2. The SOX gene family of transcription factors highly related to the SRY gene . They are characterized by the presece of a HMG domain involved in various developmental processes . The encoded proteins are capable of binding to DNA in a sequence-specific manner . In human , the deletion or mutation of SOX proteins results in developmental defects and congenital disease . It has been shown that mutations in the human SOX9 gene cause campomelic dysplasia(CD) and autosomal sex reversal, SOX10 mutation cause Waardenburg syndrome(WS) , and so on . This paper reviewed the progress of the relation between the mutation of SOX gene and disease occurrence in recent years . Part Ⅱ: Studies 1. Using PCR—SSCP technique , we analysisd SOX4 gene in 13 colorectal cancer tissues and the normal tissue beside cancer . we found mutations in 5 cases,but it wasn`t found in the normal tissues. 2. SOX gene is a new kind of development regulation gene family based on SRY gene as the basic gene member . The coding production of this gene is a kind of very important transcriptional regulation factor . Studies show that in the SOX gene family , SOX4 gene may influence the transcriptional regulation of it`s downsteam gene and cause the origination of the colorectal cancer . In this study , we cloned 5 cases of HMG–box of SOX4 gene which was found to have mutations through the PCR—SSCP check . After sequenceing , we found point mutations at 10541、10580、10476、10485、10518、10648 and 10666 bp in the HMG–box regions of SOX4 gene in 5 cases , but it was not found in normal tissue beside cancer. It suggests that the SOX4 gene mutation may be associated with the origination and development of the colorectal cancer. Our studies first reports the SOX4 gene mutation of the colorectal cancer tissues . And also provides molecular data for the study of the relations between the mutation of SOX gene and disease occurrence.更多还原