[1]田红艳,陈萍萍,李 笑,等.Gab2通过PI3K/Akt/ARK5/MMP途径影响乳腺癌的侵袭和转移[J].中国药理学通报,2015,(07):1014-1018.[doi:10.3969/j.issn.1001-1978.2015.07.025]
 TIAN Hong-yan,CHEN Ping-ping,LI Xiao,et al.Gab2 effects the invasion and metastasis of breast carcinoma through PI3K/Akt/ARK5/MMP signal pathway[J].Chinese Pharmacological Bulletin,2015,(07):1014-1018.[doi:10.3969/j.issn.1001-1978.2015.07.025]
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Gab2通过PI3K/Akt/ARK5/MMP途径影响乳腺癌的侵袭和转移()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2015年07期
页码:
1014-1018
栏目:
论 著
出版日期:
2015-07-15

文章信息/Info

Title:
Gab2 effects the invasion and metastasis of breast carcinoma through PI3K/Akt/ARK5/MMP signal pathway
作者:
田红艳1陈萍萍1李 笑2李洪利3任甜甜1张宝刚1尹崇高4刘雨清1
潍坊医学院 1.病理学教研室、2.生物科学与技术学院、3.医学研究实验中心、4.护理学院,山东 潍坊 261053
Author(s):
TIAN Hong-yan1CHEN Ping-ping1LI Xiao2LI Hong-li3 REN Tian-tian1 ZHANG Bao-gang1YIN Chong-gao4LIU Yu-qing1
1.Dept of Pathology,2.College of Biological Science and Technology,3.Medicine Research Center, 4.College of Nursing,Weifang Medical University,Weifang Shangdong 261053,China
关键词:
乳腺癌 Gab2 Akt ARK5 MMP 侵袭 转移
Keywords:
breast carcinoma Gab2 Akt ARK5 MMP invasion metastasis
分类号:
R329.25; R341; R73-37; R737.9
DOI:
10.3969/j.issn.1001-1978.2015.07.025
文献标志码:
A
摘要:
目的 探讨Gab2在乳腺浸润性导管癌侵袭和转移中的分子机制,为临床预防乳腺癌的侵袭和转移提供理论依据。方法 采用免疫组织化学SP法检测80例乳腺浸润性导管癌组织及癌旁相对正常组织(>5 cm)中Gab2蛋白表达情况,并分析其表达与乳腺浸润性导管癌临床病理参数的相关性,分析浸润性导管癌中Gab2、MMP-2及MMP-9蛋白表达的相关性。采用Western blot检测乳腺癌细胞系MCF-7、MDA-MB-231中Gab2蛋白的表达情况。采用RNAi技术将小RNA干扰质粒瞬时转染乳腺癌细胞系MDA-MB-231,应用Western blot检测转染成功后各组细胞中MMP-2和MMP-9蛋白的表达情况,应用 Transwell 体外侵袭实验检测各组细胞的侵袭性,用EGF刺激细胞后Western blot检测Akt及ARK5的磷酸化情况。结果 浸润性导管癌组织中Gab2蛋白的阳性表达率明显高于癌旁正常组织(P<0.01),浸润性导管癌中Gab2蛋白的表达与ER、组织学分期及淋巴结转移密切相关(P<0.05),且其表达与MMP-2及MMP-9蛋白的表达呈正相关; MDA-MB-231细胞系中Gab2蛋白表达量高于MCF-7细胞系中表达量; 转染干扰质粒24 h后,与转染空载细胞组相比,SiGab2/MDA-MB-231细胞组中Gab2蛋白的表达量明显降低,结果显示转染成功。同时,SiGab2/MDA-MB-231细胞组穿过Transwell小室人工基膜数量明显减少(P<0.05),并伴有MMP-2、MMP-9蛋白表达降低(P<0.05)。用EGF刺激各组细胞,结果显示:在SiGab2/MDA-MB-231细胞组Akt及ARK5的磷酸化明显受到抑制。结论 Gab2通过PI3K/Akt/ARK5信号通路影响MMP-2、MMP-9的表达从而促进乳腺癌的侵袭与转移。
Abstract:
Aim To investigate the molecular mechanism of Gab2 in the invasion and metastasis of breast cancer and provide a theoretical basis for clinical prevention of breast cancer invasion and metastasis. Methods The Gab2, MMP-2 and MMP-9 expressions in 80 cases of breast cancer were detected by immunohistochemistry. Western blot was used to detect the expression of Gab2 protein in MDA-MB-231 cells and MCF-7 cells. The siRNA plasmid was used to transfect MDA-MB-231 cells. Western blot was used to detect the proteins expression of Gab2, MMP-2 and MMP-9. Transwell in vitro experiment was used to detect the invasion ability of each group transfected MDA-MB-231 cells, Western blot was used to analyze phosphorylation of Akt and ARK5 induced by epithelial growth factor(EGF)in transfected cells(SiGab2/MDA-MB-231 and Scr/MDA-MB-231). Results The expression of Gab2 protein in invasive ductal carcinoma was significantly higher than in normal breast tissue(P<0.01). The expression of Gab2 was dramatically correlated with lymph node metastasis, ER expression, tumor histological grade, MMP-2 and MMP-9(P<0.05). The expression of Gab2 protein in MDA-MB-231 cells was higher than in MCF-7 cells. The expression of Gab2, MMP-2 and MMP-9 decreased in SiGab2/MDA-MB-231 cells and the invasion ability of SiGab2/MDA-MB-231 cells was significantly decreased(P<0.05), and after 5 minutes' stimulating by EGF, the phosphorylation of Akt and ARK5 was significantly reduced. Conclusion Gab2 can promote the invasion and metastasis of breast cancer by effecting the expression of MMP-2 and MMP-9 through PI3K/ Akt /ARK5 signal pathway.

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备注/Memo

备注/Memo:
收稿日期:2015-03-12,修回日期:2015-04-02 基金项目: 国家自然科学基金青年基金项目(No 81402389); 山东省自然科学基金(No ZR2014HL077); 山东省高等学校科技计划(No J12LK03,J13LK03); 国家级大学生创新训练计划项目(No 201410438003); 潍坊市科技计划项目(No 201302089); 潍坊医学院大学生科技创新基金(No KX2014033) 作者简介:田红艳(1989-),女,硕士,研究方向:肿瘤病理学,E-mail:tianhongyan0413@163.com; 刘雨清(1962-),女,硕士,教授,研究方向:肿瘤病理学,通讯作者,E-mail:yuqingliu89@hotmail.com; 尹崇高(1979-),男,硕士,副教授,研究方向:肿瘤病理学,通讯作者,E-mail:lihongli1213@sina.com
更新日期/Last Update: 1900-01-01