研究背景:乳腺癌是全球常見的惡性腫瘤之一,也是導(dǎo)致女性死亡的重要原因之一。作為一種異質(zhì)性疾病,其以不同的激素受體表達狀態(tài)為特征,而這些特征也常用于預(yù)測乳腺癌不同亞型的靶向治療。目前,臨床上已有多種治療乳腺癌的靶向藥物,如雌激素受體（ER）靶向藥物--他莫昔芬、HER2靶向藥物--曲妥珠單抗。以上靶向藥物雖然可有效抑制乳腺癌的演進,但侵襲和轉(zhuǎn)移仍是導(dǎo)致乳腺癌患者死亡的主要病因。因此,深入探究乳腺癌侵襲轉(zhuǎn)移的相關(guān)調(diào)控基因及分子通路作用機制,將有利于明確乳腺癌的早期診斷及治療靶點,對改善乳腺癌的個體化治療及改善患者的預(yù)后具有重要臨床價值。醌氧化還原酶（NAD（P）H:quinone oxidoreductase-1,NQO1）,也被稱為DT-硫辛酰胺脫氫酶,定位于染色體16p22。它通過受體NAD（P）H催化醌類及其衍生物,使其失去雙電子發(fā)生還原反應(yīng),避免了對細胞的損傷。值得注意的是,當(dāng)NQO1cDNA609位點發(fā)生突變時可導(dǎo)致細胞解毒致癌物的能力降低,增加致癌物的作用,導(dǎo)致某種易感個體發(fā)生惡性病變,從而增加個體罹患多種惡性腫瘤的危險。近年來,NQO1在多種惡性腫瘤中所扮演的角色備受學(xué)者的關(guān)... 

【文章來源】：延邊大學(xué)吉林省 211工程院校

【文章頁數(shù)】：106 頁

【學(xué)位級別】：博士

【文章目錄】：
中文摘要
ABSTRACT
ABBREVIATIONS
1. INTRODUCTION
2. MATERIALS AND METHODS
    2.1 Materials
        2.1.1 Experimental reagents and instruments
    2.2 Methods
        2.2.1 Cell culture
        2.2.2 Cell viability assay
        2.2.3 Transtection
        2.2.4 Stable cell line generation
        2.2.5 TCGA BC cohorts
        2.2.6 Wound healing assay
        2.2.7 Colony-forming assay
        2.2.8 EdU assay
        2.2.9 Immunofluorescence
        2.2.10 Migration assay
        2.2.11 Invasion assay
        2.2.12 Western blot
        2.2.13 Immunohistochemistry
        2.2.14 Measurement of glucose, lactate, and ATP
        2.2.15 Co-Immunoprecipitation （Co-IP）
        2.2.16 In vivo tumorigenesis and metastasis assays
        2.2.17 Statistical analysis
3. RESULTS
    3.1 NQO1 overexpression correlates with poor prognosis in BC
    3.2 NQO1 enhances tumor growth and in vivo tumorigenesis
    3.3 NQO1 induces epithelia-mesenchymal transition and promotes cellular migration and invasion
    3.4 NQO1 promoted BC cell growth and metastasis via regulating glycolysis reprogramming
    3.5 Identification of PKLR as a target gene of NQO1 in BC
    3.6 The NQO1/PKLR axis regulated the AMPK and AKT/mTOR pathways to modify BC EMT and glycolysisreprogramming
    3.7 PKLR is inversely correlated with the expression of NQO1 in normal and breast cancers
4. DISCUSSION
5. CONCLUSIONS
REFERENCES
攻讀博士學(xué)位期間取得的科研業(yè)績
致謝



本文編號：3144148