內皮細胞特異分子1於前列腺癌細胞之角色

The role of endothelial cell-specific molecule 1 in human prostate cancer cell

陳綉佩(Hsiu-Pei Chen)

指導教授 ： 謝逸憲

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2015年)

https://doi.org/10.6834/CSMU.2015.00140

摘要

在台灣前列腺癌近年來已成為男性國人惡性腫瘤的第七位，而前列腺癌死亡率居高不下。但是若能有效抑制癌細胞的增生、轉移及侵襲，將可大幅減低癌症的死亡率。因此找到前列腺癌治療的分子標的是當務之急。先前的研究證實了，ESM-1參與腫瘤的形成過程，如細胞增殖、細胞週期進程、血管新生、遷移和侵襲作用。但至今的研究對於ESM-1在人類前列腺癌的生物功能、訊息傳遞路徑和基因調節機制仍尚不清楚。因此本研究利用西方墨點法及Real- time PCR分析四株前列腺癌細胞，實驗發現PC3細胞株其內生性ESM-1蛋白表現量較高。為了釐清ESM-1在前列腺癌中扮演何種角色，利用shESM-1抑制人類前列腺癌細胞株PC3的ESM-1蛋白表達後，以MTT方法分析、群落生長形成及西方墨點法方法分析，證實了當抑制ESM-1蛋白表現時，會促進PC3細胞產生增殖情形，同時增加cyclin D1和抑制p21蛋白表現。細胞移動和侵襲能力實驗也證實抑制ESM-1蛋白表現會促進其PC3細胞移動和侵襲。此外，也發現當抑制ESM-1蛋白時，會造成MMP9和MMP13的蛋白量上升。另外，異種移植PC3細胞之動物模式證實抑制ESM-1會促進前列腺癌腫瘤形成。綜合以上論點證實人類前列腺癌細胞中ESM-1扮演一個抑制癌症發展的角色，未來可望能利用ESM-1在人類前列腺癌的預後指標，來作為分子標靶治療平台，應用在治療抗癌模式。

關鍵字

前列腺癌 ； 內皮細胞特異分子1

並列摘要

In recent years, Taiwan has become the male prostate cancer people seventh, and prostate cancer mortality rates.If we can inhibit cancer cell proliferation, metastasis and invasion, will significantly reduce cancer mortality. So finding prostate cancer molecular target is a priority. Previous studies have confirmed, ESM-1 involved in tumor formation, such as cell proliferation, cell cycle progression, angiogenesis, migration and invasion effect.However, studies to date for ESM-1 in human prostate cancer biological functions, signaling pathways and gene regulation mechanisms remain unclear.Therefore, this study, western blot and Real- time PCR analysis of three strains of varying degrees of differentiation of prostate cancer cell lines, PC3 cell line was found that the higher their endogenous ESM-1 protein expression.ESM-1 in order to clarify what role in prostate cancer, we use shESM-1 inhibition ESM-1 protein expression in human prostate cancer cell line PC3 to MTT Assay, cell cycle analysis and colony forming test, it was confirmed that when suppression ESM-1 protein expression, it will promote the human prostate cancer cell line PC3 generate growth scenario.In the cell migration experiments confirmed that when inhibition ESM-1 protein expression can promote cancer cell migration role.The results also found that when the inhibition of ESM-1 protein, can cause increased activity of MMP9 and MMP13, whether and promote tumor growth corresponding relationship.Based on the above argument was confirmed in human prostate cancer cells ESM-1 plays a role in suppressing the development of cancer, with the results of this study, the future is expected to be able to take advantage of ESM-1 in human prostate cancer biological functions, signaling pathways and prognosis indicators as molecular targeted therapy platform, used in the treatment of anti-cancer mode.

並列關鍵字

prostate cancer ； endothelial cell-specific molecule 1

參考文獻

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