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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 investigate the effect of gelsolin (GSN) on the growth of esophageal alpha (alpha) (ERa) positive and human epidermal growth factor receptor 2 (Her2) overexpressing breast cancer cell line MCF7 / Her2. Methods The eukaryotic expression vector of GSN was constructed and stably transfected into MCF7 / Her2 cells. The breast cancer cell line MCF7 / Her2 / GSN stably overexpressing GSN was identified by RT-PCR and Western Blot. The expression of Her2, tissue inhibitor of metalloproteinase-3 (TIMP3) and the expression of TIMP3 were detected by Western Blot and RT-PCR, compared with that of MCF7 / Her2 / V transfected with empty vector. Extracellular regulated protein kinase (ERK) activation, to explore the underlying mechanism of action. Results After stable expression of GSN, MCF7 / Her2 cells showed morphological changes, proliferation, migration and invasion. The results showed that the expression of Her2 was down and the expression of TIMP3 was up-regulated. However, ERK activation induced by estrogen in MCF7 / Her2 cells was reversed . Conclusion Gelsolin can reduce the expression of Her2 and inhibit the proliferation and migration of breast cancer MCF7 / Her2 cells by down-regulating the activation of ERK and up-regulating the expression of TIMP3.