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  本文關(guān)鍵詞： 核糖核酸酶抑制因子 胰島素樣生長因子 蛋白質(zhì)相互作用 腫瘤 免疫共沉淀　出處：《大連醫(yī)科大學(xué)》2006年碩士論文　論文類型：學(xué)位論文

【摘要】： 核糖核酸酶抑制因子(Ribonuclease Inhibitor, RI)是一種胞漿內(nèi)酸性蛋白質(zhì),分子量約為50KDa。RI是核糖核酸酶A(Ribonuclease A, RNase A)的抑制劑,可以有效地抑制其對RNA的水解作用。RI也是血管生成因子(Angiogenin,Ang)的高效抑制劑。血管生成因子具有強烈的促進(jìn)新生血管形成活性,而腫瘤生長與新生血管密切相關(guān),因此Ang的存在有利于腫瘤細(xì)胞的生長。RI與Ang結(jié)合后可以抑制Ang的促血管生成活性,從而抑制腫瘤生長。RI由含有許多亮氨酸重復(fù)順序的多肽組成,含有這樣重復(fù)順序的一百多種蛋白質(zhì)顯示了廣泛的功能,包括細(xì)胞周期調(diào)節(jié)、DNA修復(fù)、對細(xì)胞外基質(zhì)的相互作用以及抑制酶活性等。RI定位于染色體的11p15.5,同樣位于此位置的胰島素樣生長因子(IGF-2)是促有絲分裂原,它不僅是通過旁分泌與自分泌形式調(diào)節(jié)細(xì)胞生長、分化、凋亡和轉(zhuǎn)化的多肽,而且是信號傳導(dǎo)通路中重要的刺激因子。上述各種過程的失衡促使細(xì)胞增殖失控,進(jìn)而導(dǎo)致惡變。有證據(jù)證明IGF-2在許多腫瘤細(xì)胞中可使細(xì)胞增殖增加,抑制凋亡,增加局部浸潤和轉(zhuǎn)移。另外有研究[27]觀察到IGF-2可以直接促進(jìn)臍靜脈內(nèi)皮細(xì)胞生成Angiogenic(血管生成素),從而促進(jìn)新生血管的形成。RI與IGF-2位于人染色體同一位置附近,而具有截然相反的生理作用。故而,推測二者可能存在某種相互作用關(guān)系,并進(jìn)一步探討研究RI在信號傳導(dǎo)中的重要生理作用,從而為RI的抗腫瘤,抗血管生成作用提供重要的理論依據(jù)。 本研究的目的在于探討真核細(xì)胞系中過表達(dá)RI對IGF-2的影響,并進(jìn)一步了解二者相互作用關(guān)系,以其闡明RI抗腫瘤、抗氧化的作用機理。本試驗將人核糖核酸酶抑制因子(hRI)通過逆轉(zhuǎn)錄病毒載體(pLNCX-RI)經(jīng)過病毒包裝細(xì)胞(PA317)包裝后的高滴度病毒上清,感染真核細(xì)胞:人乳腺癌(MCF-7)細(xì)胞系,經(jīng)G418篩選后,
[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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：R341

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相關(guān)期刊論文 前2條

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本文編號：1503528