【摘要】：乳腺癌是嚴(yán)重危害女性健康的惡性腫瘤。研究發(fā)現(xiàn): HER2蛋白(HER2)的表達(dá)與乳腺癌的發(fā)生、轉(zhuǎn)移和預(yù)后密切相關(guān)。正常情況下,HER2在乳腺上皮細(xì)胞和其他正常細(xì)胞有低水平表達(dá)。約有25-30%的乳腺癌患者的腫瘤細(xì)胞高水平表達(dá)HER2,此外,高表達(dá)HER2的乳腺癌患者易產(chǎn)生耐藥性并多有不良的預(yù)后。因此,HER2可能成為乳腺癌免疫治療的靶點(diǎn)。 結(jié)核分支桿菌熱休克蛋白65(HSP65)具有分子伴侶及分子佐劑的作用。在抗腫瘤的免疫應(yīng)答過程中,HSP65可激活機(jī)體的非特異性免疫系統(tǒng),并可引導(dǎo)與其形成復(fù)合物或與之融合的抗原肽在樹突狀細(xì)胞內(nèi)經(jīng)MHCI類途徑加工遞呈,從而激活抗原特異性的細(xì)胞毒性T淋巴細(xì)胞( CTLs )。 我們將HSP65與HER2的表位肽基因相連接,并在大腸桿菌中成功地表達(dá)了熱休克蛋白65-HER2多表位融合蛋白(HSP65-HER2)。獲得純化的HSP65-HER2后,我們研究了HSP65-HER2的生物學(xué)功能。人體外實(shí)驗(yàn)表明:經(jīng)HSP65-HER2誘導(dǎo)的T淋巴細(xì)胞可通過特異性及非特異性的免疫機(jī)制抑制HER2陽性腫瘤細(xì)胞的生長。小鼠體內(nèi)實(shí)驗(yàn)表明:HSP65-HER2能夠誘導(dǎo)對HER2陽性腫瘤細(xì)胞的特異性殺傷。因此,HSP65-HER2可能成為一種對HER2陽性乳腺癌有預(yù)防或治療價(jià)值的新的生物制劑。
[Abstract]:Breast cancer is a malignant tumor that seriously endangers the health of women. It is found that the expression of HER2 protein (HER2) is closely related to the occurrence, metastasis and prognosis of breast cancer. Under normal conditions, HER2 is expressed at low level in breast epithelial cells and other normal cells. About 25-30% of breast cancer patients expressed HER2, at high level. In addition, breast cancer patients with high expression of HER2 were prone to develop drug resistance and poor prognosis. Therefore, HER2 may be the target of immunotherapy for breast cancer. Mycobacterium tuberculosis heat shock protein 65 (HSP65) has molecular chaperone and molecular adjuvant. In the process of anti-tumor immune response, HSP65 can activate the body's non-specific immune system, and can lead to the formation of complex or fusion of antigenic peptides in dendritic cells via MHCI pathway. Thus activating antigen-specific cytotoxic T lymphocyte (CTLs). We linked HSP65 with the epitope peptide gene of HER2 and successfully expressed the heat shock protein 65-HER2 multiepitope fusion protein (HSP65-HER2) in Escherichia coli. After obtaining purified HSP65-HER2, we studied the biological function of HSP65-HER2. In vitro human body experiments showed that T lymphocytes induced by HSP65-HER2 could inhibit the growth of HER2 positive tumor cells through specific and non-specific immune mechanisms. In vivo experiments in mice showed that HSP65-HER2 could induce specific killing of HER2 positive tumor cells. Therefore, HSP65-HER2 may become a new biological agent with preventive or therapeutic value for HER2-positive breast cancer.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R341

【參考文獻(xiàn)】

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1 李玉保,付旭彬,鮑恩東;熱休克蛋白研究進(jìn)展[J];畜牧與獸醫(yī);2004年11期

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