CD24通过FAK-PI3K通路影响乳腺癌侵袭转移的研究

发布时间：2018-05-23 10:53

本文选题：乳腺癌 + CD24　；参考：《青岛大学》2016年博士论文

【摘要】：第一部分CD24和FAK-PI3K信号通路相关蛋白在乳腺浸润性导管癌中的表达及其临床意义目的:探讨CD24和FAK-PI3K信号通路相关蛋白在乳腺浸润性导管癌中的表达及其临床意义。方法:应用免疫组化SP法检测乳腺浸润性导管癌组织中CD24、p-FAK、p-AKT的表达水平,以及与临床病理参数之间的相关性,同时分析CD24与p-FAK、p-AKT表达水平的相关性。结果:CD24表达与淋巴结转移、组织学分级、Ki-67表达具有明显的相关性(P0.05),但其表达与年龄、肿瘤大小、激素受体(ER/PR)、HER-2无明显相关性(p0.05);p-FAK表达与淋巴结转移、Ki-67表达具有明显的相关性(P0.05),但其表达与年龄、肿瘤大小、组织学分级、激素受体(ER/PR)、HER-2无明显相关性(p0.05);p-AKT表达与淋巴结转移、Ki-67表达具有明显的相关性(P0.05),但其表达与年龄、肿瘤大小、组织学分级、激素受体(ER/PR)、HER-2无明显相关性(p0.05)。进一步研究CD24、p-FAK、p-AKT在乳腺癌组织中的表达的相关性发现CD24表达水平与p-FAK、p-AKT表达水平具有明显的相关性。结论:CD24、p-FAK、p-AKT过表达与乳腺浸润性导管癌增殖转移密切相关,CD24可能通过激活FAK-PI3K信号通路影响肿瘤增殖转移。第二部分抑制CD24表达对乳腺癌细胞MCF-7增殖、侵袭转移能力及对三苯氧胺处理的影响目的:探讨CD24对MCF-7细胞增殖、侵袭转移能力的影响及对三苯氧胺处理的影响方法:通过CD24 si RNA抑制MCF-7细胞CD24的表达,Western blot检测CD24、ER表达水平,Western blot检测不同浓度的TAM处理的MCF-7细胞CD24、ER表达水平。通过MTT、ELISA、TUNEL检测CD24 si RNA对MCF-7细胞活力、凋亡以及对三苯氧胺敏感性的影响。通过划痕实验、细胞侵袭实验检测CD24 si RNA转染MCF-7细胞的侵袭转移能力。结果:转染CD24 si RNA显著抑制CD24的表达,与对照细胞相比,CD24抑制后MCF-7细胞增殖、侵袭转移能力受到明显的抑制,凋亡细胞显著增加。CD24抑制导致MCF-7细胞对TAM敏感性增强。结论:CD24基因敲低能够显著降低乳腺癌MCF-7细胞增殖、侵袭转移能力,促进细胞凋亡,并且可提高MCF-7细胞对TAM敏感性。第三部分CD24通过FAK-PI3K信号通路影响乳腺癌细胞MCF-7增殖、侵袭转移的研究目的:探讨CD24影响乳腺癌细胞MCF-7增殖、侵袭转移的机制方法:通过p CDNA3.1(+)-CD24质粒转染乳腺癌MCF-7细胞,应用Western blot检测转染效果。应用PI3K特异性抑制剂LY294002处理CD24过表达MCF-7细胞,Western blot检测CD24、p-FAK、p-AKT表达水平,通过划痕实验、细胞侵袭实验检测MCF-7细胞的侵袭转移能力。结果:与对照细胞相比,转染p CDNA3.1(+)-CD24质粒显著增强CD24的表达,CD24过表达后,p-FAK、p-AKT表达水平明显升高,细胞侵袭转移能力明显的增强。应用PI3K特异性抑制剂LY294002可降低p-AKT的表达水平,细胞侵袭转移能力降低。结论:CD24可通过激活FAK-PI3K通路影响乳腺癌细胞MCF-7的侵袭转移能力。
[Abstract]:Part 1 expression and clinical significance of CD24 and FAK-PI3K signaling related proteins in invasive ductal carcinoma of the breast and its clinical significance: To explore the expression and clinical significance of CD24 and FAK-PI3K signaling related proteins in invasive ductal carcinoma of the breast. Methods: immunohistochemical SP method was used to detect CD24, p-FAK, P in invasive ductal carcinoma of breast. The expression level of -AKT and the correlation with the clinicopathological parameters and the correlation between the expression of CD24 and p-FAK and p-AKT. Results: CD24 expression has a significant correlation with lymph node metastasis, histological grading and Ki-67 expression (P0.05), but the expression has no significant correlation with age, tumor size, hormone receptor (ER/PR) and HER-2 (p0.0). 5): p-FAK expression has a significant correlation with lymph node metastasis and Ki-67 expression (P0.05), but its expression has no significant correlation with age, tumor size, histological grade, hormone receptor (ER/PR), HER-2 (P0.05); p-AKT expression has a significant correlation with lymph node metastasis, Ki-67 expression (P0.05), but its expression and age, tumor size, histological score Level, hormone receptor (ER/PR), HER-2 without significant correlation (P0.05). Further study of the correlation of CD24, p-FAK, p-AKT expression in breast cancer tissue found that CD24 expression level has a significant correlation with p-FAK, p-AKT expression level. Conclusion: CD24, p-FAK, p-AKT over table is closely related to the proliferation and metastasis of invasive ductal carcinoma of the breast. Over activation of FAK-PI3K signaling pathway affects tumor proliferation and metastasis. The second part inhibits the proliferation of MCF-7, invasion and metastasis and the effect on tamoxifen treatment in breast cancer cells: the effect of CD24 on the proliferation of MCF-7 cells, the ability of invasion and metastasis and the effect of CD24 on the location of tamoxifen: the inhibition of MCF-7 fine by CD24 Si RNA The expression of cell CD24, Western blot detection of CD24, ER expression level, Western blot detection of MCF-7 cell CD24, ER expression level of different concentrations of TAM. The invasion and metastasis ability of -7 cells. Results: transfection of CD24 Si RNA significantly inhibited the expression of CD24. Compared with the control cells, the proliferation of MCF-7 cells and the invasion and transfer ability were significantly inhibited compared with the control cells. The apoptotic cells significantly increased the inhibition of.CD24 to increase the sensitivity of MCF-7 cells to TAM. Conclusion: CD24 gene knockdown can significantly reduce the breast cancer MC. F-7 cell proliferation, invasion and metastasis ability, promote cell apoptosis, and improve the sensitivity of MCF-7 cells to TAM. Third part CD24 affects the proliferation and invasion of breast cancer cells through FAK-PI3K signaling pathway. The purpose of this study is to explore the mechanism of CD24 affecting MCF-7 proliferation and invasion and metastasis of breast cancer cells: P CDNA3.1 (+) -CD24 plasmid Transfection of breast cancer MCF-7 cells and using Western blot to detect the transfection effect. PI3K specific inhibitor LY294002 was used to treat CD24 over expression of MCF-7 cells. Western blot detected CD24, p-FAK, p-AKT expression level, and the invasion and metastasis ability of cells was detected by scratch test and cell invasion test. +) -CD24 plasmid significantly enhanced the expression of CD24. After CD24 overexpression, the expression level of p-FAK, p-AKT was obviously increased and the cell invasion and metastasis was obviously enhanced. The application of PI3K specific inhibitor LY294002 could reduce the expression level of p-AKT and decrease the ability of cell invasion and metastasis. Conclusion: CD24 can affect MCF-7 of breast cancer cells by activating FAK-PI3K pathway. Invasion and metastasis.
【学位授予单位】：青岛大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.9

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