凝溶胶蛋白抑制乳腺癌细胞MCF7/Her2增殖及迁移侵袭的作用  

Gelsolin inhibits proliferation and migration /invasion of breast cancer cell line MCF7/Her2

作　　者：赵元茵[1] 顿国栋[1] 张钊[1] 柳鹏[1] 于杰[1] Shiuan Chen 李渝萍[1] 

机构地区：[1]第三军医大学生物化学与分子生物学教研室,重庆400038 [2]Beckman Research Institute,City of Hope,National Medical Center,duarteca91010

出　　处：《遵义医学院学报》2014年第1期48-52,共5页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:81072155)

摘　　要：目的研究凝溶胶蛋白(gelsolin,GSN)对雌激素受体α(ERα)阳性、人表皮生长因子受体2(Her2)过表达乳腺癌细胞MCF7/Her2生长的作用。方法构建GSN的真核表达载体,并稳定转染MCF7/Her2细胞,以RT-PCR及Western Blot鉴定得到稳定过表达GSN的乳腺癌细胞系MCF7/Her2/GSN。以空载体转染的稳定表达细胞MCF7/Her2/V作对照,比较其细胞形态、增殖和迁移能力的改变;Western Blot及RT-PCR检测Her2、组织金属蛋白酶抑制剂-3(TIMP3)表达和细胞外调节蛋白激酶(ERK)的活化,探索深层次的作用机制。结果 MCF7/Her2稳定过表达GSN后,细胞形态改变且增殖及迁移、侵袭能力明显低于对照细胞;发现Her2表达下降,TIMP3的表达上调,而雌激素导致的MCF7/Her2细胞ERK活化增强被逆转。结论凝溶胶蛋白能降低Her2的表达,并通过下调ERK的活化及上调TIMP3的表达,抑制乳腺癌细胞MCF7/Her2增殖及迁移侵袭作用。Objective To study the function of gelsolin （GSN） in ERa positive, Her2 high expression breast cancer cell MCFT/Her2. Methods Constructed a gelsolin expression plasmid. Established a gelsolin stable - overexpression cell line by stable transfection with hygromycin selection. The cell line was identified of the GSN overexpression by RT -PCR and Western Blot. Cell morphology, cell growth and ability of migration/invasion of GSN overexpression cell line were compared to the control vector transfected ceils and the parental cell line. Her2, TIMP3 expression and the ERK activation were studied by real -time RT -PCR and Western Blot. Re- suits Cell morphology of GSN overexpression cells was changed and the proliferation and migration/invasion were inhibited in GSN overexprssion cells. Conclusion Gelsolin may inhibit the proliferation and migration/invasion of MCFT/Her2 cells by reducing expression of Her2, increasing expression of TIMP3 and inhibiting the ERα non - genomic activity. It is demonstrated that GSN can reverse the proliferation and migration/invasion caused by Her2.

关 键 词：凝溶胶蛋白 乳腺癌 Her2 增殖 迁移侵袭 

分 类 号：R73-361[医药卫生—肿瘤]