TGF-β1诱导人前列腺癌PC3细胞上皮间叶化的研究  

TGF-β1-induced Epithelial-mesenchymel Transition in Human Prostate Cancer Cells PC3

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作  者:陈丹扬[1] 刘浩[1] 王昊[1] 王险峰[1] 杜军[1] 

机构地区:[1]中山大学药学院微生物与生化药学实验室,广州510006

出  处:《中国细胞生物学学报》2013年第6期768-773,共6页Chinese Journal of Cell Biology

基  金:国家重点基础研究发展计划(973)项目(批准号:2011CB935803);国家自然科学基金(批准号:81071712;81272311)资助的课题~~

摘  要:上皮细胞间叶化(epithelial-mesenchymal transition,EMT)与肿瘤侵袭转移密切相关,转化生长因子-β(transforming growth factor-beta,TGF-β)已被证实为肿瘤EMT的主要诱导剂。该研究旨在探讨TGF-β1对人前列腺癌PC3细胞EMT发生的诱导作用。经TGF-β1处理的PC3细胞,在相差倒置显微镜下观察到细胞形态由上皮型向间叶型转化;细胞划痕和Transwell实验检测细胞的迁移能力较对照组显著增强;Real-time PCR、Western blot和细胞免疫荧光验证TGF-β1能上调间叶型标记蛋白的表达及下调上皮型标志蛋白的表达。进一步发现,TGF-β1对转录因子Snail的表达没有明显的影响,但是能促进Snail的入核,干扰Snail能逆转TGF-β1对PC3细胞EMT发生的诱导作用。该研究表明,TGF-β1能够介导Snail的入核而激活Snail,促进前列腺癌PC3细胞的发生。It has been proved that epithelial-mesenchymal transition (EMT) is correlated with tumor invasion and metastasis. Transforming growth factor-beta (TGF-β) has been identified as a main inducer of EMT. The aim of this study is to investigate the effects of TGF-β1 on EMT in human prostate cancer PC3 cells. We found that TGF-β1 treatment could induce morphological alteration of PC3 cells from epithelial morphology to mesenchymal morphology. Wound healing assay and Transwell assay showed that TGF-β1 significantly increases the migration of PC3 cells. Real-time PCR, Western blot and immunoflurescence staining demonstrated that TGF-β1 up-regulates the expression of mesenchymal makers and down-regulates epithelial markers. Furthermore, TGF-β1 treatment does not alter the expression of Snail, but promotes Snail nuclear localization. Interestingly, knockdown of Snail by siRNA dramatically attenuates TGF-β1-induced EMT. These results demonstrated that TGF-β1 could induce EMT in PC3 cells by promoting Snail nuclear localization.

关 键 词:TGF-Β1 上皮细胞间叶化 SNAIL 前列腺癌 

分 类 号:R737.25[医药卫生—肿瘤]

 

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