转录因子HMBOX1与高级别浆液性卵巢癌发生发展之间的关系

发布时间：2018-03-23 18:32

本文选题：HMBOX1　切入点：上皮性卵巢癌　出处：《山东大学》2017年硕士论文

【摘要】：目的卵巢癌作为常见的妇女生殖器官癌症之一,由于缺乏有效的早期诊疗手段和较易发生远处转移,其死亡率仍高居妇科癌症之首,5年生存率很低。依据组织学类型的不同,上皮性卵巢癌可分为浆液性癌、黏液性癌、子宫内膜样癌、透明细胞癌、移行细胞癌等类型。在上皮性卵巢癌不同类型中,浆液性卵巢癌最为常见。高级别浆液性卵巢癌是上皮性卵巢癌中常见的一种。传统的研究观点认为卵巢癌起源于卵巢上皮组织,近年来有研究提出高级别浆液性卵巢癌很可能来自远端的输卵管上皮。鉴于高级别浆液性卵巢癌是卵巢癌患者死亡的主要原因,明确高级别浆液性卵巢癌发病的机制以及寻找针对卵巢癌的新的治疗靶点已成为妇科肿瘤研究中一项有价值而且有必要的任务。同源异形盒基因作为一类转录调节因子在调控胚胎调控组织器官发育以及细胞的增殖和生长过程中起着重要作用。近年来研究显示,同源异形盒基因还参与某些肿瘤的发生、发展,其中肝细胞核因子(HNF)家族基因和癌症关系的研究正逐渐引起人们的注意。HMBOX1基因是HNF家族的成员。HMBOX1基因高度保守,与HNF家族其他分子有很高的同源性。研究证实HMBOX1基因广泛表达于人体至少18种组织器官。研究发现,HMBOX1表达增高可能通过NKG2D/DAP10信号通路抑制NK细胞的杀伤活性。HMBOX1在骨髓间质细胞向血管内皮细胞的分化过程中起着关键的调控作用。有研究指出HMBOX1可能与肿瘤发生有关,但是关于HMBOX1与卵巢癌之间关系的研究尚未有报道。本研究目的在于检测HMBOX1在高级别浆液性卵巢癌中的表达,并研究不同上皮性卵巢癌细胞系中HMBOX1的表达量与卵巢癌细胞生物学行为之间是否相关,为进一步探索HMBOX1的功能及其与卵巢癌发生发展之间的关系奠定基础。方法1.运用实时荧光定量PCR技术、Western blot技术和免疫组化技术检测正常卵巢上皮、正常输卵管伞上皮、交界性浆液性卵巢肿瘤和高级别浆液性卵巢癌组织中HMBOX1的表达水平。运用荧光定量PCR技术和Western blot技术检测了卵巢正常上皮细胞系(HOSEpiC)和上皮性卵巢癌细胞系(H08910,A2780和SKOV3)中HMBOX1的表达量。2.采用MTT实验检测细胞增殖能力,采用平板克隆实验检测细胞克隆形成能力。为了检测细胞侵袭和迁移能力,我们分别采用了 Transwell基质胶实验和细胞划痕实验,并采用流式细胞术来检测细胞周期。3.运用实时荧光定量PCR技术检测细胞周期调控基因的相对表达量。结果1.与正常卵巢上皮组织相比,HMBOX1在高级别浆液性卵巢癌组织中呈低表达;与正常上皮细胞系HOSEpiC相比,HMBOX1在卵巢癌细胞系H08910和A2780中的表达水平较低。2.通过观察不同细胞系的生物学行为,我们发现不同细胞中HMBOX1的表达量与细胞的增殖能力有一定的相关性,而与细胞迁移和细胞侵袭能力无关。3.HMBOX1可能与卵巢癌细胞周期调控基因Cyclin D1、Cyclin E1呈一定的相关性。结论HMBOX1可能通过调节细胞周期调控基因来调节上皮性卵巢癌细胞的增殖行为,从而参与调控高级别浆液性卵巢癌的发生、发展的分子机制。
[Abstract]:Objective: ovarian cancer is one of the common cancers in women of reproductive organs, due to the lack of effective means of early diagnosis and more prone to distant metastasis, the mortality rates are among the highest in gynecological cancer first, 5 year survival rate is very low. According to histological types, epithelial ovarian cancer can be divided into serous carcinoma, mucinous carcinoma. Endometrioid carcinoma, clear cell carcinoma, transitional cell carcinoma and other types. In different types of epithelial ovarian cancer, ovarian cancer is the most common. High-grade serous ovarian cancer is epithelial ovarian cancer is a common research. The traditional view that ovarian cancer originated from epithelial ovarian tissue. In recent years studies have suggested high-grade serous ovarian cancer is likely to come from the distal tubal epithelium. In high-grade serous ovarian cancer is the leading cause of death in patients with ovarian cancer, clear high-grade serous ovarian cancer and the mechanism In order to find a new therapeutic target for ovarian cancer has become a valuable and necessary task of gynecologic oncology research. The homeobox gene as a transcription factor in the regulation of embryonic tissue development and regulation of cell proliferation and growth plays an important role in the process. Recent studies have shown that homeobox some gene is also involved in tumor occurrence, development, including hepatocyte nuclear factor (HNF) gene family and cancer research is gradually attracted the attention of people is a member of the.HMBOX1.HMBOX1 gene of the HNF gene family is highly conserved, have high homology with HNF family molecules. Other studies have confirmed that HMBOX1 gene is widely expressed in the human body at least 18 kinds of tissues and organs. The study found that increased HMBOX1 expression may inhibit the cytotoxicity of.HMBOX1 NK cells via NKG2D/DAP10 signaling pathway in bone marrow stromal cells into vascular endothelial cells Play a key role in the process of cell differentiation. Studies have shown that HMBOX1 may be associated with tumorigenesis, but the study on the relationship between HMBOX1 and ovarian cancer have not been reported. The purpose of this study is to detect the expression of HMBOX1 in high-grade serous ovarian carcinoma, and the relationship between HMBOX1 in different epithelial ovarian cancer cell gene expression and biological behavior of ovarian cancer cells, to further explore the function of HMBOX1 in ovarian cancer and the relationship between the development of the foundation. The 1. methods using real-time fluorescence quantitative PCR technology, Western blot technology and immunohistochemical detection of normal ovarian tissues, normal fallopian tube epithelium, the expression level of HMBOX1 junction serous ovarian tumors and high-grade serous ovarian carcinoma. Using fluorescence quantitative PCR and Western blot was detected in normal ovarian epithelium Cell line (HOSEpiC) and epithelial ovarian carcinoma cell lines (H08910, A2780 and SKOV3) expression of.2. HMBOX1 in the experimental ability of MTT cell proliferation was assayed by using cell cloning, cloning test plate forming ability. In order to detect cell invasion and migration ability, we use the Transwell matrix test and cell scratch test. Also used to detect the cell cycle of.3. using the relative expression of real-time fluorescence quantitative PCR detection of cell cycle regulation of gene flow cytometry. Results 1. and normal ovarian epithelial tissues compared with HMBOX1 showed low expression in high-grade serous ovarian carcinoma; HOSEpiC compared with normal epithelial cells, the expression level of H08910 and HMBOX1 in A2780 is low in.2. through the biological behavior of different cell lines of ovarian cancer cell lines, we found that the expression of HMBOX1 and cell proliferation in different cells There is a certain correlation, but not.3.HMBOX1 may be related to ovarian cancer cell cycle regulation gene Cyclin and D1 cell migration and cell invasion was correlated to Cyclin E1. Conclusion HMBOX1 may regulate the proliferation of cell cycle genes to regulate epithelial ovarian cancer cells, which are involved in the regulation of high-grade serous ovarian cancer and the molecular mechanism of the development.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.31

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