人核糖核酸酶抑制因子对胰岛素样生长因子Ⅱ的影响及其机理的研究

发布时间：2018-02-11 16:47

本文关键词： 核糖核酸酶抑制因子胰岛素样生长因子蛋白质相互作用肿瘤免疫共沉淀　出处：《大连医科大学》2006年硕士论文　论文类型：学位论文

【摘要】： 核糖核酸酶抑制因子(Ribonuclease Inhibitor, RI)是一种胞浆内酸性蛋白质,分子量约为50KDa。RI是核糖核酸酶A(Ribonuclease A, RNase A)的抑制剂,可以有效地抑制其对RNA的水解作用。RI也是血管生成因子(Angiogenin,Ang)的高效抑制剂。血管生成因子具有强烈的促进新生血管形成活性,而肿瘤生长与新生血管密切相关,因此Ang的存在有利于肿瘤细胞的生长。RI与Ang结合后可以抑制Ang的促血管生成活性,从而抑制肿瘤生长。RI由含有许多亮氨酸重复顺序的多肽组成,含有这样重复顺序的一百多种蛋白质显示了广泛的功能,包括细胞周期调节、DNA修复、对细胞外基质的相互作用以及抑制酶活性等。RI定位于染色体的11p15.5,同样位于此位置的胰岛素样生长因子(IGF-2)是促有丝分裂原,它不仅是通过旁分泌与自分泌形式调节细胞生长、分化、凋亡和转化的多肽,而且是信号传导通路中重要的刺激因子。上述各种过程的失衡促使细胞增殖失控,进而导致恶变。有证据证明IGF-2在许多肿瘤细胞中可使细胞增殖增加,抑制凋亡,增加局部浸润和转移。另外有研究[27]观察到IGF-2可以直接促进脐静脉内皮细胞生成Angiogenic(血管生成素),从而促进新生血管的形成。RI与IGF-2位于人染色体同一位置附近,而具有截然相反的生理作用。故而,推测二者可能存在某种相互作用关系,并进一步探讨研究RI在信号传导中的重要生理作用,从而为RI的抗肿瘤,抗血管生成作用提供重要的理论依据。本研究的目的在于探讨真核细胞系中过表达RI对IGF-2的影响,并进一步了解二者相互作用关系,以其阐明RI抗肿瘤、抗氧化的作用机理。本试验将人核糖核酸酶抑制因子(hRI)通过逆转录病毒载体(pLNCX-RI)经过病毒包装细胞(PA317)包装后的高滴度病毒上清,感染真核细胞:人乳腺癌(MCF-7)细胞系,经G418筛选后,
[Abstract]:Ribonuclease inhibitor (RI) is an acidic cytoplasmic protein with a molecular weight of about 50 KDa.RI is an inhibitor of ribonuclease A (RNase A). RI is also an effective inhibitor of angiogenesis factor Angiogenin Ang.Angiogenic factor has a strong activity to promote angiogenesis, and tumor growth is closely related to angiogenesis. Therefore, the existence of Ang is beneficial to the growth of tumor cells. RI can inhibit the angiogenic activity of Ang after binding with Ang, and thus inhibit tumor growth. RI is composed of polypeptides containing a lot of leucine repeats. More than 100 proteins with this repetitive sequence show a wide range of functions, including cell cycle regulation of DNA repair, Ri is located at chromosome 11p15.5and insulin-like growth factor IGF-2 (also located at this position) is a mitogen, which not only regulates cell growth through paracrine and autocrine forms, but also regulates cell growth by paracrine and autocrine. Peptides that differentiate, apoptosis, and transform, and are important stimulators in signal transduction pathways. The imbalance in these processes causes cell proliferation to get out of control. There is evidence that IGF-2 can increase cell proliferation and inhibit apoptosis in many tumor cells. In addition, it has been observed that IGF-2 can directly promote the formation of angiogenetic (Angiogenic) (angiogenin) in endothelial cells of umbilical vein, thus promoting the formation of neovascularization. RI and IGF-2 are located near the human chromosome. Therefore, we speculate that there may be some kind of interaction relationship between the two, and further study the important physiological role of RI in signal transduction, so as to be the anti-tumor of RI. Anti-angiogenesis provides an important theoretical basis. The purpose of this study was to investigate the effect of overexpression of RI on IGF-2 in eukaryotic cell lines, and to further understand the interaction between the two in order to elucidate the anti-tumor effect of RI. The mechanism of antioxidation. The high titer virus supernatant of human ribonuclease inhibitor hRI, which was packaged by retrovirus vector pLNCX-RI through viral packaging cell line PA317), was infected with eukaryotic cells: human breast cancer cell line MCF-7.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R341

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