PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up-regulates CA9 expression.
PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up-regulates CA9 expression.
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PADI4 刺激食管鳞状细胞癌肿瘤生长并上调 CA9 表达。
DOI：
10.1002/mc.22907
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发表时间：
2019-01
影响因子：
4.6
通讯作者：
Chang X
中科院分区：
文献类型：
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作者：
Liu C;Tang J;Li C;Pu G;Yang D;Chang X
越来越多的证据表明肽基精氨酸脱亚胺酶同工型4（PADI 4）在肿瘤发生中起重要作用。然而，PADI 4对荷瘤小鼠的影响尚不清楚，也没有研究在动物模型中研究这种致瘤途径。在本研究中，用表达PADI4的慢病毒转染食管鳞状细胞癌（ESCC）的ECA109细胞，并将其注射到BALB/c裸鼠体内。在用过表达PADI 4的ECA109细胞建立的小鼠肿瘤中，肿瘤大小和重量显著增加。PCR阵列分析显示，在用PADI 4表达质粒转染的ECA109细胞中，CA9表达增加，而在用抗PADI 4 siRNA转染的细胞中检测到CA9表达水平降低。此外，在用PADI 4过表达细胞建立的小鼠肿瘤中检测到CA9表达上调。免疫组织化学检测到与邻近非肿瘤组织和正常组织对照相比，ESCC组织中PADI 4和CA 9的表达和共定位增加。使用Western印迹验证这些结果。在分别用表达PADI4的质粒或抗PADI4 siRNA转染的ECA109和EC9706（另一种ESCC起源细胞系）细胞中，细胞增殖显著增加或减少。上述研究结果表明，ESCC中PADI 4表达增加刺激肿瘤生长并上调CA9表达，已知其促进肿瘤细胞的转移特性。
An increasing amount of evidence indicates that peptidylarginine deiminase isoform 4 (PADI4) plays an important role in tumorigenesis. However, the effects of PADI4 on tumor‐bearing mice are unknown, and no studies have investigated this tumorigenic pathway in an animal model. In the present study, ECA109 cells originating from esophageal squamous cell carcinoma (ESCC) were transfected with PADI4‐expressing lentivirus and were injected into BALB/c nude mice. Tumor size and weight were significantly increased in the mouse tumors established with PADI4‐overexpressing ECA109 cells. PCR array analysis revealed increased CA9 expression in ECA109 cells transfected with a PADI4‐expressing plasmid, while decreased CA9 expression levels were detected in cells transfected with anti‐PADI4 siRNA. Furthermore, up‐regulation of CA9 expression was detected in mouse tumors established with PADI4‐overexpressing cells. Immunohistochemistry detected the increased expression and co‐localization of PADI4 and CA9 in ESCC tissues compared with adjacent non‐tumor tissues and normal tissue controls. These results were verified using Western blotting. Cell proliferation significantly increased or decreased in ECA109 and EC9706 (another ESCC‐originating cell line) cells transfected with a PADI4‐expressing plasmid or anti‐PADI4 siRNA, respectively. The above findings suggest that increased PADI4 expression in ESCC stimulates tumor growth and up‐regulates CA9 expression, which is known to promote metastatic properties in tumor cells.
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影响因子：
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作者：
Zheng Y;Zhao G;Xu B;Liu C;Li C;Zhang X;Chang X
通讯作者：
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影响因子：
3.8
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Shen Z
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3
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Mohanan S;Cherrington BD;Horibata S;McElwee JL;Thompson PR;Coonrod SA
通讯作者：
Coonrod SA
影响因子：
5.8
作者：
Chang X;Fang K
通讯作者：
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影响因子：
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