本文選題：HMBOX1　切入點(diǎn)：上皮性卵巢癌　出處：《山東大學(xué)》2017年碩士論文

【摘要】：目的卵巢癌作為常見(jiàn)的婦女生殖器官癌癥之一,由于缺乏有效的早期診療手段和較易發(fā)生遠(yuǎn)處轉(zhuǎn)移,其死亡率仍高居?jì)D科癌癥之首,5年生存率很低。依據(jù)組織學(xué)類型的不同,上皮性卵巢癌可分為漿液性癌、黏液性癌、子宮內(nèi)膜樣癌、透明細(xì)胞癌、移行細(xì)胞癌等類型。在上皮性卵巢癌不同類型中,漿液性卵巢癌最為常見(jiàn)。高級(jí)別漿液性卵巢癌是上皮性卵巢癌中常見(jiàn)的一種。傳統(tǒng)的研究觀點(diǎn)認(rèn)為卵巢癌起源于卵巢上皮組織,近年來(lái)有研究提出高級(jí)別漿液性卵巢癌很可能來(lái)自遠(yuǎn)端的輸卵管上皮。鑒于高級(jí)別漿液性卵巢癌是卵巢癌患者死亡的主要原因,明確高級(jí)別漿液性卵巢癌發(fā)病的機(jī)制以及尋找針對(duì)卵巢癌的新的治療靶點(diǎn)已成為婦科腫瘤研究中一項(xiàng)有價(jià)值而且有必要的任務(wù)。同源異形盒基因作為一類轉(zhuǎn)錄調(diào)節(jié)因子在調(diào)控胚胎調(diào)控組織器官發(fā)育以及細(xì)胞的增殖和生長(zhǎng)過(guò)程中起著重要作用。近年來(lái)研究顯示,同源異形盒基因還參與某些腫瘤的發(fā)生、發(fā)展,其中肝細(xì)胞核因子(HNF)家族基因和癌癥關(guān)系的研究正逐漸引起人們的注意。HMBOX1基因是HNF家族的成員。HMBOX1基因高度保守,與HNF家族其他分子有很高的同源性。研究證實(shí)HMBOX1基因廣泛表達(dá)于人體至少18種組織器官。研究發(fā)現(xiàn),HMBOX1表達(dá)增高可能通過(guò)NKG2D/DAP10信號(hào)通路抑制NK細(xì)胞的殺傷活性。HMBOX1在骨髓間質(zhì)細(xì)胞向血管內(nèi)皮細(xì)胞的分化過(guò)程中起著關(guān)鍵的調(diào)控作用。有研究指出HMBOX1可能與腫瘤發(fā)生有關(guān),但是關(guān)于HMBOX1與卵巢癌之間關(guān)系的研究尚未有報(bào)道。本研究目的在于檢測(cè)HMBOX1在高級(jí)別漿液性卵巢癌中的表達(dá),并研究不同上皮性卵巢癌細(xì)胞系中HMBOX1的表達(dá)量與卵巢癌細(xì)胞生物學(xué)行為之間是否相關(guān),為進(jìn)一步探索HMBOX1的功能及其與卵巢癌發(fā)生發(fā)展之間的關(guān)系奠定基礎(chǔ)。方法1.運(yùn)用實(shí)時(shí)熒光定量PCR技術(shù)、Western blot技術(shù)和免疫組化技術(shù)檢測(cè)正常卵巢上皮、正常輸卵管傘上皮、交界性漿液性卵巢腫瘤和高級(jí)別漿液性卵巢癌組織中HMBOX1的表達(dá)水平。運(yùn)用熒光定量PCR技術(shù)和Western blot技術(shù)檢測(cè)了卵巢正常上皮細(xì)胞系(HOSEpiC)和上皮性卵巢癌細(xì)胞系(H08910,A2780和SKOV3)中HMBOX1的表達(dá)量。2.采用MTT實(shí)驗(yàn)檢測(cè)細(xì)胞增殖能力,采用平板克隆實(shí)驗(yàn)檢測(cè)細(xì)胞克隆形成能力。為了檢測(cè)細(xì)胞侵襲和遷移能力,我們分別采用了 Transwell基質(zhì)膠實(shí)驗(yàn)和細(xì)胞劃痕實(shí)驗(yàn),并采用流式細(xì)胞術(shù)來(lái)檢測(cè)細(xì)胞周期。3.運(yùn)用實(shí)時(shí)熒光定量PCR技術(shù)檢測(cè)細(xì)胞周期調(diào)控基因的相對(duì)表達(dá)量。結(jié)果1.與正常卵巢上皮組織相比,HMBOX1在高級(jí)別漿液性卵巢癌組織中呈低表達(dá);與正常上皮細(xì)胞系HOSEpiC相比,HMBOX1在卵巢癌細(xì)胞系H08910和A2780中的表達(dá)水平較低。2.通過(guò)觀察不同細(xì)胞系的生物學(xué)行為,我們發(fā)現(xiàn)不同細(xì)胞中HMBOX1的表達(dá)量與細(xì)胞的增殖能力有一定的相關(guān)性,而與細(xì)胞遷移和細(xì)胞侵襲能力無(wú)關(guān)。3.HMBOX1可能與卵巢癌細(xì)胞周期調(diào)控基因Cyclin D1、Cyclin E1呈一定的相關(guān)性。結(jié)論HMBOX1可能通過(guò)調(diào)節(jié)細(xì)胞周期調(diào)控基因來(lái)調(diào)節(jié)上皮性卵巢癌細(xì)胞的增殖行為,從而參與調(diào)控高級(jí)別漿液性卵巢癌的發(fā)生、發(fā)展的分子機(jī)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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.31

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