本文選題：Cyclin + D1�。� 參考：《吉林大學(xué)》2008年碩士論文

【摘要】： 細胞周期蛋白Cyclin D1和周期蛋白依賴性蛋白激酶抑制劑p16分別是細胞周期G1/S轉(zhuǎn)換的正負調(diào)節(jié)因子。在正常情況下,Cyclin D1和p16保持平衡,但在腫瘤細胞中,卻存在Cyclin D1的過量表達和p16的廣泛失活。由于Cyclin D1的過量表達和p16的失活在腫瘤細胞中同時存在,而且它們的下游分子都是CDK4/6,所以同時抑制Cyclin D1的活性和恢復(fù)p16的功能,可以使對CDK4/6的抑制作用得到疊加,因此開展它們的聯(lián)合治療可能是一個可行的基因治療策略。 胞內(nèi)抗體技術(shù)是基于抗體工程和胞內(nèi)信號傳導(dǎo)而衍生出來一項新的實現(xiàn)細胞內(nèi)重要靶蛋白表型敲除的技術(shù)。在實驗中,我們將前期構(gòu)建的靶向Cyclin D1的內(nèi)質(zhì)網(wǎng)滯留型的胞內(nèi)抗體基因和野生型p16基因分別單獨和聯(lián)合導(dǎo)入Cyclin D1過量表達和p16純合缺失的MCF-7細胞中。實驗發(fā)現(xiàn),這些外源基因在細胞中都得到表達,并且表達的胞內(nèi)抗體能與細胞內(nèi)的Cyclin D1結(jié)合。同時發(fā)現(xiàn),它們的轉(zhuǎn)染都能引起細胞G1期的阻滯,誘導(dǎo)細胞凋亡和抑制細胞增殖,而且聯(lián)合轉(zhuǎn)染比單獨轉(zhuǎn)染效果更顯著。這為基因的聯(lián)合治療開辟了新的途徑,具有一定的應(yīng)用價值。
[Abstract]:Cyclin D1 and cyclin dependent protein kinase inhibitor p16 are positive and negative regulators of cell cycle G1 / S transition, respectively. Under normal conditions, Cyclin D1 and p16 remain in balance, but in tumor cells, there is overexpression of Cyclin D1 and widespread inactivation of p16. Because the overexpression of Cyclin D1 and the inactivation of p16 exist simultaneously in tumor cells and their downstream molecules are CDK4 / 6, the inhibition of the activity of Cyclin D1 and the restoration of p16 function at the same time can result in the superposition of the inhibitory effect on CDK4 / 6. Therefore, the development of their combined therapy may be a feasible gene therapy strategy. Intracellular antibody technology is a new technique based on antibody engineering and intracellular signal transduction to realize the knockout of important target protein phenotypes in cells. In the experiment, the previously constructed endoplasmic reticulum (ER) retention type antibody gene and wild-type p16 gene were introduced into MCF-7 cells with overexpression of Cyclin D1 and homozygous deletion of p16, respectively. It was found that these exogenous genes were expressed in cells, and the expressed intracellular antibodies could bind to Cyclin D1. It was also found that their transfection could induce G1 phase arrest, induce apoptosis and inhibit cell proliferation, and the effect of co-transfection was more significant than that of single transfection. This opens up a new way for gene combination therapy and has certain application value.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R392;R730.5

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本文編號：2044252