【摘要】：第一部分FOXC2促進(jìn)多形性腦膠質(zhì)母細(xì)胞瘤增殖、遷移與侵襲作用及其機(jī)制研究 目的：揭示FOXC2(forkhead box C2,叉頭框C2)在GBM (Glioblastoma,多形性膠質(zhì)母細(xì)胞瘤)組織及GBM細(xì)胞系中的表達(dá)情況并利用GBM細(xì)胞系構(gòu)建FOXC2高表達(dá)細(xì)胞模型與FOXC2基因沉默細(xì)胞模型。檢測(cè)FOXC2對(duì)于GBM細(xì)胞增殖，遷移及侵襲能力的影響并研究該影響在GBM細(xì)胞內(nèi)的調(diào)節(jié)機(jī)制。 方法：利用RT-PCR、Western blot以及免疫組織化學(xué)實(shí)驗(yàn)測(cè)定GBM人腦組織樣本、對(duì)照人腦組織樣本以及六種GBM細(xì)胞系中FOXC2的表達(dá)情況。根據(jù)所得六種GBM細(xì)胞系中FOXC2表達(dá)結(jié)果，進(jìn)一步通過(guò)質(zhì)粒轉(zhuǎn)染與RNA基因沉默實(shí)驗(yàn)構(gòu)建FOXC2高表達(dá)的SNB19-FOXC2細(xì)胞模型、FOXC2基因沉默的T98G-shFOXC2細(xì)胞模型及EGFR(epidermal growth factor receptor,表皮生長(zhǎng)因子)沉默的SNB19-FOXC2-siEGFR細(xì)胞模型。應(yīng)用MTT和細(xì)胞克隆形成實(shí)驗(yàn)測(cè)定上述所構(gòu)建細(xì)胞系中FOXC2表達(dá)對(duì)SNB19和T98G細(xì)胞增殖能力的影響并通過(guò)細(xì)胞傷口愈合實(shí)驗(yàn)和Boyden小室模型測(cè)定SNB19-FOXC2細(xì)胞與T98G-shFOXC2的遷移及侵襲能力變化。通過(guò)RT-PCR、Western blot和免疫組化實(shí)驗(yàn)測(cè)定FOXC2對(duì)EGFR在GBM細(xì)胞系中表達(dá)量的影響。同時(shí)在SNB19-FOXC2細(xì)胞中構(gòu)建EGFR基因沉默模型SNB19-FOXC2-siEGFR1,2。通過(guò)MTT實(shí)驗(yàn)，Boyden小室模型實(shí)驗(yàn)，細(xì)胞傷口愈合實(shí)驗(yàn)，研究EGFR對(duì)于FOXC2促GBM細(xì)胞增殖，遷移以及侵襲能力的調(diào)控作用。 結(jié)果：分別將10份GBM病人大腦樣本與10份對(duì)照病人大腦樣本的RT-PCR和Western blot實(shí)驗(yàn)結(jié)果比較得出所有GBM病人大腦樣本中FOXC2的表達(dá)量都明顯高于對(duì)照病人大腦樣本。免疫組化實(shí)驗(yàn)結(jié)果中也發(fā)現(xiàn)GBM病人大腦樣本中的FOXC2陽(yáng)性細(xì)胞數(shù)也同樣高于對(duì)照病人腦組織樣本。在U87, T98G, SNB19,SW1088, SF767和SW1783六種GBM細(xì)胞系中，T98G中FOXC2表達(dá)量最高而SNB19中FOXC2的表達(dá)量最低。根據(jù)此結(jié)果，進(jìn)一步將T98G細(xì)胞用于FOXC2基因沉默實(shí)驗(yàn)構(gòu)建T98G-shFOXC2細(xì)胞模型，而將SNB19細(xì)胞用于FOXC2基因轉(zhuǎn)染實(shí)驗(yàn)，構(gòu)建FOXC2基因高表達(dá)SNB19-FOXC2模型。MTT和細(xì)胞克隆形成實(shí)驗(yàn)結(jié)果顯示，SNB19-FOXC2細(xì)胞相對(duì)與對(duì)照組SNB19細(xì)胞增殖能力大幅提高，克隆形成總數(shù)明顯增多，克隆形成范圍更廣。而T98G-shFOXC2細(xì)胞相對(duì)與對(duì)照組T98G細(xì)胞克隆形成數(shù)目明顯減少，克隆形成范圍也明顯縮小。細(xì)胞傷口愈合實(shí)驗(yàn)和Boyden小室實(shí)驗(yàn)結(jié)果顯示，SNB19-FOXC2細(xì)胞能夠顯著加快細(xì)胞傷口愈合速度并且具有2倍于SNB19細(xì)胞穿透Transwell膜的能力。另一方面，F(xiàn)OXC2基因沉默后，T98G-shFOXC2細(xì)胞遷移與侵襲的能力顯著降低并且T98G-shFOXC2細(xì)胞對(duì)于細(xì)胞傷口愈合的促進(jìn)作用以及透過(guò)Transwell膜的能力都明顯小于T98G細(xì)胞。RT-PCR及Western blot實(shí)驗(yàn)結(jié)果顯示，F(xiàn)OXC2基因沉默能夠明顯降低T98G細(xì)胞中EGFR在RNA轉(zhuǎn)錄和蛋白水平的表達(dá)。利用RNA干擾技術(shù)，進(jìn)一步沉默SNB19-FOXC2細(xì)胞中EGFR相關(guān)基因，構(gòu)建SNB19-FOXC2-siEGFR細(xì)胞模型。MTT實(shí)驗(yàn)，，Boyden小室模型實(shí)驗(yàn)及細(xì)胞傷口愈合實(shí)驗(yàn)結(jié)果顯示，SNB19-FOXC2-siEGFR細(xì)胞的增殖、遷移與侵襲的能力都較SNB19-FOXC2細(xì)胞有大幅的下滑。該結(jié)果說(shuō)明EGFR基因在FOXC2促進(jìn)GBM細(xì)胞的增殖、遷移與侵襲能力的發(fā)揮過(guò)程中起著重要的調(diào)控作用。 結(jié)論：（1）FOXC2在GBM病人組織樣本及GBM細(xì)胞系中為顯著高表達(dá)。（2）FOXC2在GBM細(xì)胞增殖、遷移與侵襲過(guò)程中起到至關(guān)重要的作用。（3）FOXC2調(diào)控EGFR在GBM細(xì)胞中的表達(dá)（4）EGFR是FOXC2調(diào)控GBM細(xì)胞增殖、遷移與侵襲的重要調(diào)控因子。 第二部分MUC4粘蛋白上調(diào)表皮生長(zhǎng)因子受體表達(dá)及其對(duì)多型性膠質(zhì)母細(xì)胞瘤增殖、遷移與侵襲促進(jìn)作用研究 目的：探究MUC4(mucin4,4型粘蛋白)在GBM病人組織與GBM細(xì)胞系中表達(dá)情況。構(gòu)建MUC4高表達(dá)與MUC4基因沉默細(xì)胞模型。揭示MUC4對(duì)于GBM細(xì)胞增殖、遷移及侵襲活性的影響及其分子機(jī)制。 方法：通過(guò)RT-PCR、免疫組化以及Western blot實(shí)驗(yàn)測(cè)定對(duì)照病人腦組織樣品、GBM病人腦組織樣品與六種GBM細(xì)胞系中MUC4表達(dá)量高低。根據(jù)六種GBM細(xì)胞中MUC4的表達(dá)情況進(jìn)而通過(guò)基因轉(zhuǎn)染與RNA干擾實(shí)驗(yàn)構(gòu)建MUC4過(guò)表達(dá)SNB19-MUC4細(xì)胞、MUC4沉默T98G-shMUC4細(xì)胞模型及EGFR (epidermal growthfactor receptor,表皮生長(zhǎng)因子)沉默SNB19-MUC4-siEGFR細(xì)胞模型。利用MTT和細(xì)胞克隆形成實(shí)驗(yàn)測(cè)定MUC4對(duì)GBM細(xì)胞增殖能力影響。通過(guò)傷口愈合實(shí)驗(yàn)和Boyden小室模型測(cè)定SNB19-MUC4細(xì)胞以及T98G-shMUC4細(xì)胞的遷移及侵襲能力。通過(guò)RT-PCR、Western blot和免疫組化實(shí)驗(yàn)測(cè)定MUC4對(duì)EGFR表達(dá)的影響。同時(shí)構(gòu)建EGFR基因沉默SNB19-MUC4-siEGFR1,2,3細(xì)胞模型。通過(guò)MTT實(shí)驗(yàn)，Boyden小室模型實(shí)驗(yàn)，細(xì)胞愈合實(shí)驗(yàn)，研究EGFR沉默后MUC4促GBM細(xì)胞增殖，遷移以及侵襲能力的變化情況。 結(jié)果： RT-PCR實(shí)驗(yàn)測(cè)定11份對(duì)照病人大腦樣本與11份GBM病人大腦樣本中MUC4的表達(dá)發(fā)現(xiàn)，11份GBM病人大腦樣本中MUC4的表達(dá)明顯高于對(duì)照大腦樣本并且在免疫組織化學(xué)實(shí)驗(yàn)結(jié)果中GBM病人大腦樣本中的MUC4陽(yáng)性細(xì)胞數(shù)也同樣明顯多于對(duì)照樣本。利用RT-PCR及Western blot實(shí)驗(yàn)測(cè)定了六種GBM細(xì)胞系中MUC4的表達(dá)量，結(jié)果顯示其中T98G細(xì)胞系中MUC4表達(dá)量最高而SNB19細(xì)胞系中MUC4的表達(dá)量最低，進(jìn)而將T98G細(xì)胞用于構(gòu)建MUC4基因沉默T98G-shMUC4細(xì)胞模型而將SNB19細(xì)胞用于MUC4基因轉(zhuǎn)染實(shí)驗(yàn)構(gòu)建MUC4基因過(guò)表達(dá)SNB19-MUC4細(xì)胞模型。在細(xì)胞增殖實(shí)驗(yàn)中，MTT和細(xì)胞克隆形成實(shí)驗(yàn)結(jié)果顯示SNB19-MUC4細(xì)胞相對(duì)于對(duì)照組SNB19細(xì)胞增殖能力大幅提高，克隆數(shù)量更多且克隆范圍更廣。另一方面，T98G-shMUC細(xì)胞相對(duì)與照組T98G細(xì)胞克隆數(shù)量明顯下降，范圍上也有所縮小。細(xì)胞傷口愈合實(shí)驗(yàn)證明SNB19-MUC4細(xì)胞能夠顯著加快細(xì)胞傷口愈合速度。Boyden小室模型結(jié)果顯示SNB19-MUC4細(xì)胞具有3倍與對(duì)照組細(xì)胞透過(guò)Transwell膜的能力。然而，細(xì)胞傷口愈合實(shí)驗(yàn)與Boyden小室模型結(jié)果說(shuō)明經(jīng)MUC4基因沉默后T98G-shMUC4細(xì)胞對(duì)于傷口愈合的促進(jìn)作用以及透過(guò)Transwell膜的能力都明顯小于未沉默組細(xì)胞。RT-PCR及Western blot實(shí)驗(yàn)結(jié)果顯示，MUC4基因沉默能夠明顯降低T98G細(xì)胞中EGFR在RNA和蛋白水平的表達(dá)。利用RNA干擾技術(shù)，進(jìn)一步將SNB19-MUC4細(xì)胞中EGFR相關(guān)基因EGFR-1,2,3沉默。MTT實(shí)驗(yàn)，Boyden小室模型實(shí)驗(yàn)，細(xì)胞愈合實(shí)驗(yàn)結(jié)果顯示，SNB19-MUC4細(xì)胞的增殖、遷移與侵襲的能力都較沉默前有大幅的下降。說(shuō)明EGFR基因在MUC4促進(jìn)GBM細(xì)胞的增殖、遷移與侵襲能力的過(guò)程中發(fā)揮重要的調(diào)控作用。 結(jié)論：（1）MUC4在GBM細(xì)胞系中顯著表達(dá)并且在GBM細(xì)胞的增殖、遷移與侵襲過(guò)程中發(fā)揮重要作用。（2）MUC4能夠調(diào)控EGFR在GBM細(xì)胞中的表達(dá)，EGFR對(duì)于MUC4促進(jìn)GBM細(xì)胞的增殖、遷移與侵襲能力有重要的影響。
[Abstract]:Part one: FOXC2 promotes the proliferation, migration and invasion of glioblastoma multiforme and its mechanism.
AIM: To investigate the expression of FOXC2 (forkhead box C2) in GBM (Glioblastoma multiforme glioblastoma) tissues and GBM cell lines, and to construct FOXC2 high expression cell model and FOXC2 gene silencing cell model using GBM cell lines. The regulation mechanism in GBM cells.
METHODS: The expression of FOXC2 in GBM human brain tissue samples was detected by RT-PCR, Western blot and immunohistochemical assay, and compared with human brain tissue samples and six GBM cell lines. 2 cell model, T98G-shFOXC2 cell model with FOXC2 gene silencing and SNB19-FOXC2-siEGFR cell model with EGFR (epidermal growth factor receptor) silencing. MTT and clone formation assay were used to determine the effect of FOXC2 expression on the proliferation of SNB19 and T98G cells and cell injury. The migration and invasiveness of SNB19-FOXC2 cells and T98G-shFOXC2 cells were measured by oral healing test and Boyden cell model. The effect of FOXC2 on EGFR expression in GBM cell lines was determined by RT-PCR, Western blot and immunohistochemistry. The EGFR gene silencing model SNB19-FOXC2-siEGFR1,2 was constructed in SNB19-FOXC2 cells by MTT. The effects of EGFR on FOXC2-induced proliferation, migration and invasion of GBM cells were studied by Boyden cell model and wound healing test.
Results: The expression of FOXC2 in brain samples of 10 GBM patients was significantly higher than that of 10 control patients by RT-PCR and Western blot. The number of FOXC2 positive cells in brain samples of GBM patients was also found by immunohistochemistry. In U87, T98G, SNB19, SW1088, SF767 and SW1783 GBM cell lines, the expression of FOXC2 was the highest in T98G and the lowest in SNB19. According to this result, T98G cells were further used in FOXC2 gene silencing experiment to construct T98G-shFOXC2 cell model, while SNB19 cells were used in FOXC2 gene silencing experiment. The results of MTT and cell cloning showed that the proliferation ability of SNB19-FOXC2 cells was greatly improved, the total number of cloning formation was significantly increased, and the range of cloning formation was wider. Cell wound healing test and Boyden chamber test showed that SNB19-FOXC2 cells significantly accelerated wound healing and had the ability to penetrate Transwell membrane twice as fast as SNB19 cells. On the other hand, after FOXC2 gene was silenced, T98G-shFOXC2 cells showed significant migration and invasion ability. The results of RT-PCR and Western blot showed that FOXC2 gene silencing could significantly reduce the expression of EGFR at RNA transcription and protein levels in T98G cells. EGFR-related genes in B19-FOXC2 cells were used to construct SNB19-FOXC2-siEGFR cell model. MTT, Boyden chamber and wound healing experiments showed that the proliferation, migration and invasion of SNB19-FOXC2-siEGFR cells were significantly lower than those of SNB19-FOXC2 cells. It plays an important regulatory role in the process of proliferation, migration and invasion.
CONCLUSION: (1) FOXC2 is highly expressed in GBM tissues and GBM cell lines. (2) FOXC2 plays an important role in the proliferation, migration and invasion of GBM cells. (3) FOXC2 regulates the expression of EGFR in GBM cells. (4) EGFR is an important regulator of GBM cell proliferation, migration and invasion.
Part 2 MUC4 mucin up-regulates the expression of epidermal growth factor receptor and promotes the proliferation, migration and invasion of glioblastoma multiforme
Objective: To investigate the expression of MUC4 (mucin 4,4 mucin) in GBM tissues and GBM cell lines, and to construct a cell model of MUC4 overexpression and MUC4 gene silencing.
METHODS: The expression of MUC4 in brain tissue samples of GBM patients and six GBM cell lines was determined by RT-PCR, immunohistochemistry and Western blot. According to the expression of MUC4 in six GBM cells, the over-expressed SNB19-MUC4 cells were constructed by gene transfection and RNA interference, and T98G-shM was silenced by MUC4. UC4 cell model and EGFR (epidermal growth factor receptor) silencing SNB19-MUC4-siEGFR cell model. MTT and cell clone formation assays were used to determine the effect of MUC4 on the proliferation of GBM cells. The effect of MUC4 on EGFR expression was determined by RT-PCR, Western blot and immunohistochemical staining. The SNB19-MUC4-siEGFR 1,2,3 cell model with EGFR gene silencing was constructed. The proliferation, migration and invasiveness of GBM cells after EGFR silencing were studied by MTT test, Boyden cell model test and cell healing test.
Results: The expression of MUC4 in 11 brain samples of GBM patients and 11 brain samples of GBM patients was detected by RT-PCR. The expression of MUC4 in 11 brain samples of GBM patients was significantly higher than that in control brain samples, and the number of MUC4 positive cells in brain samples of GBM patients was also significantly higher than that in control brain samples. The expression of MUC4 in six GBM cell lines was measured by RT-PCR and Western blot. The results showed that MUC4 was the highest in T98G cell line and the lowest in SNB19 cell line. T98G cells were used to construct mutant T98G-shMUC4 cell model and SNB19 cells were used to construct MUC4 gene transfection experiment. In cell proliferation experiments, MTT and cell clone formation assays showed that SNB19-MUC4 cells had significantly higher proliferation capacity, more clones and a wider range of clones than the control group. On the other hand, T98G-shMUC cells had significantly lower number of clones than the control group T98G cells. Cell wound healing experiments showed that SNB19-MUC4 cells significantly accelerated wound healing. Boyden's compartment model showed that SNB19-MUC4 cells had three times the ability of control and control cells to penetrate Transwell membranes. The results of RT-PCR and Western blot showed that MUC4 gene silencing could significantly reduce the expression of EGFR at RNA and protein levels in T98G cells. SNB19-MUC4 cells were further treated with RNA interference technique. EGFR-1,2,3 gene was silenced. MTT test, Boyden chamber model test and cell healing test showed that the proliferation, migration and invasion of SNB19-MUC4 cells were significantly decreased compared with those before silencing.
Conclusion: (1) MUC4 is highly expressed in GBM cells and plays an important role in the proliferation, migration and invasion of GBM cells. (2) MUC4 can regulate the expression of EGFR in GBM cells. EGFR plays an important role in the proliferation, migration and invasion of GBM cells.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.41

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王先祥,馮春國(guó),李長(zhǎng)元;人腦膠質(zhì)瘤腫瘤標(biāo)志物研究現(xiàn)狀[J];安徽醫(yī)學(xué);2004年06期

2 ;Role of DJ-1-induced PTEN down-regulation in migration and invasion of human glioma cells[J];癌癥;2010年12期

3 鐘巍;Cetuximab治療非小細(xì)胞肺癌的進(jìn)展[J];癌癥進(jìn)展;2005年02期

4 方琦;趙革靈;羅學(xué)忠;許成杰;;腦膠質(zhì)瘤中p16與p53及增殖細(xì)胞核抗原蛋白的表達(dá)和意義[J];中國(guó)醫(yī)師雜志;2006年07期

5 陳真;陳智偉;;西妥昔單抗對(duì)非小細(xì)胞肺癌細(xì)胞的體外抑制作用[J];中國(guó)肺癌雜志;2010年08期

6 馮勇智;表皮生長(zhǎng)因子受體與肺癌[J];國(guó)外醫(yī)學(xué)(內(nèi)科學(xué)分冊(cè));2004年01期

7 申景嶺,張小玲;TGF-β/Smads信號(hào)轉(zhuǎn)導(dǎo)途徑與腫瘤發(fā)生發(fā)展的研究進(jìn)展[J];國(guó)外醫(yī)學(xué).遺傳學(xué)分冊(cè);2003年03期

8 趙蔭農(nóng);何妮;歐超;曹驥;劉劍勇;袁衛(wèi)平;吳飛翔;黃山;;乳腺良、惡性病變中EGFR、EGFRvⅢ的表達(dá)及其臨床意義[J];廣西醫(yī)科大學(xué)學(xué)報(bào);2008年01期

9 鐘寶元;劉艷秀;;腫瘤中STAT3、P-STAT3的表達(dá)及與EMT關(guān)系的研究進(jìn)展[J];贛南醫(yī)學(xué)院學(xué)報(bào);2013年04期

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